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1.
PLoS One ; 12(8): e0182799, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28813492

RESUMO

BACKGROUND: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea. RESULTS: 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009). CONCLUSIONS: The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.


Assuntos
Clostridioides difficile , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecção Hospitalar , Hospitais , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Biomarcadores , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Comorbidade , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Grécia/epidemiologia , Instalações de Saúde , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Sensibilidade e Especificidade
2.
AIDS Rev ; 17(4): 191-201, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26616844

RESUMO

With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients.


Assuntos
Complexo AIDS Demência/prevenção & controle , Terapia Antirretroviral de Alta Atividade , Doenças Cardiovasculares/prevenção & controle , Infecções por HIV/terapia , Inflamação/terapia , Fator de Ativação de Plaquetas/uso terapêutico , Complexo AIDS Demência/imunologia , Complexo AIDS Demência/fisiopatologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Terapia Combinada , Comorbidade , Progressão da Doença , Comportamento Alimentar , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Terapia de Alvo Molecular
3.
Lipids Health Dis ; 13: 90, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24884881

RESUMO

BACKGROUND: Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients. METHODS: Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures. RESULTS: Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen. CONCLUSIONS: Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Alcinos , Animais , Benzoxazinas/uso terapêutico , Ciclopropanos , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Fator de Ativação de Plaquetas/metabolismo , Tenofovir , Fator de Necrose Tumoral alfa/metabolismo
4.
Angiology ; 63(5): 343-52, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21948973

RESUMO

Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory processes, is also implicated in endothelial dysfunction during human immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of naive male patients, 8 with early HIV infection (group A) and 17 just before treatment initiation (group B), versus 18 healthy age-matched males (group C). Statistical analysis was performed with 1-way analysis of variance (ANOVA) criterion and Pearson r test. Higher PAF biosynthesis in patients' leukocytes versus group C was accompanied by an increase in lipoprotein-associated phospholipase A2 (Lp-PLA2) activity that degrades PAF. Moreover, PAF synthesis was higher and Lp-PLA2 activity was lower in group B compared to group A. Lipoprotein-associated phospholipase A2 was positively correlated with viral load and negatively correlated with CD4 cell counts in group B. The activities of PAF-basic biosynthetic enzymes in patients' leukocytes were also negatively correlated with CD4 cell counts. The observed continuous increase in PAF biosynthesis during HIV infection progress seems to amplify the risk of AIDS manifestations and/or cardiovascular complications in HIV-infected patients, while a subsequent increase in Lp-PLA2 activity seems to be a host response.


Assuntos
Enzimas/sangue , Infecções por HIV/sangue , Infecções por HIV/enzimologia , Leucócitos/enzimologia , Fator de Ativação de Plaquetas/análise , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Acetiltransferases/sangue , Adulto , Análise de Variância , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Diacilglicerol Colinofosfotransferase/sangue , Grécia , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipases A2/sangue , Valor Preditivo dos Testes , RNA Viral/sangue , Carga Viral
5.
AIDS Res Hum Retroviruses ; 28(8): 766-75, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22050695

RESUMO

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Fator de Ativação de Plaquetas/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Contagem de Linfócito CD4 , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Combinação de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Masculino , Organofosfonatos/farmacologia , Oxazinas/farmacologia , Carga Viral
6.
J Inflamm (Lond) ; 8: 17, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21736752

RESUMO

BACKGROUND: Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. METHODS: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. RESULTS: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. CONCLUSIONS: These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.

7.
AIDS Res Hum Retroviruses ; 24(8): 1079-86, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18620493

RESUMO

Platelet-activating factor (PAF) is a potent inflammatory mediator, which seems to play a role in the pathogenesis of several AIDS manifestations such as AIDS dementia complex, Kaposi's sarcoma, and HIV-related nephropathy. PAF antagonists have been studied in these conditions with promising results. In order to examine the possible interactions between PAF and antiretroviral therapy, we studied the effect of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors against PAF biological activities and its basic biosynthetic enzymes dithiothreitol-insensitive PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), as well as its main degradative enzyme PAF-acetylhydrolase, of human mesangial cell line (HMC). We also studied the effect of several backbones and highly active antiretroviral therapy (HAART) regimens against PAF activity. Among the drugs tested, several inhibited PAF-induced platelet aggregation in a concentration-depended manner, with tenofovir, efavirenz, and ritonavir exhibiting the higher inhibitory effect. In addition, when these drugs were combined in backbones and HAART regimens based on American antiretroviral therapy proposals, they also synergistically exhibited an inhibitory effect against PAF-induced platelet aggregation. Several of these drugs have also inhibited in vitro microsomal PAF-CPT activity, and concentrations of lopinavir-r or tenofovir-DF (similar to their IC(50) against PAF-induced platelet aggregation) exhibited the same effect against PAF-CPT and Lyso-PAF-AT when added in the cell medium of cultured HMC. In addition, in naïve patients treated with one of the most potent anti-PAF HAART regimens (efavirenz/emtricitabine/tenofovir-DF) for a period of 1 month, a significant reduction of the specific activity of PAF-CPT of washed human leukocytes of these patients was also observed, compared with its levels before the HAART treatment. These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Fator de Ativação de Plaquetas/efeitos dos fármacos , 1-Alquil-2-acetilglicerofosfocolina Esterase/efeitos dos fármacos , Acetiltransferases/efeitos dos fármacos , Células Cultivadas , Diacilglicerol Colinofosfotransferase/efeitos dos fármacos , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Agregação Plaquetária/efeitos dos fármacos
8.
Transfusion ; 44(1): 59-66, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14692968

RESUMO

BACKGROUND: One HIV-1 and HCV assay simultaneously detects HIV-1 and HCV RNA (Procleix, Chiron Corp.). The main intended use of the assay is the testing of blood and blood products in blood banking. STUDY DESIGN AND METHODS: To evaluate the clinical sensitivity of the assay, 164 anti-HIV-1+ and 160 anti-HCV+ patients of different viral load were tested. The assay specificity was determined in 1000 HIV-1- and HCV-seronegative blood donors. The ability of the assay to detect different HCV genotypes was investigated in a total of 40 patients of different genotypes (1-4). Furthermore, to investigate the reduction of the HCV window phase before seroconversion, serial samples of 25 hemodialysis patients who seroconverted to anti-HCV were also tested. RESULTS: The assay detected all 60 HIV-1-infected patients with a viral load of greater than 50 copies per mL and 48 of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60 patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients with a viral load of less than 50 IU per mL tested positive. The assay specificity was found to be 100 percent. In addition, all 40 patients of different HCV genotypes were successfully detected. Finally, the median time that the assay detected HCV infection before second- and third-generation anti-HCV assay was found to be 183 and 91 days, respectively. CONCLUSION: The assay sensitivity and specificity, its ability to detect different HCV genotypes, and the significant reduction of window period of HCV infection further support its use for improving the safety of blood and blood products.


Assuntos
HIV-1/genética , Hepacivirus/genética , RNA Viral/análise , Virologia/métodos , Anticorpos Antivirais/análise , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/imunologia , Hepacivirus/imunologia , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Sensibilidade e Especificidade , Fatores de Tempo , Carga Viral
9.
Hormones (Athens) ; 2(1): 43-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-17003001

RESUMO

Data on body composition changes in HIV infected patients is sparse and controversial. The aim of this study was to assess body composition in asymptomatic HIV-infected men with normal body weight in comparison to healthy HIV-negative control men and to investigate possible body composition changes in HIV-positive patients over a 2-year observation period. One hundred eight asymptomatic seropositive men, aged 19-62 years, and 20 healthy sex, age and weight - matched controls were recruited for the cross-sectional part of the study. Fifty-eight of the HIV+ patients were followed up for 2 years. Body weight, BMI, Bone Mineral Content (BMC), body Fat mass (Fat), % Fat, body Lean mass (Lean) and % Lean was recorded for each subject at the beginning and at the end of the follow-up period. The same analysis was repeated separately for arms, trunk and legs. HIV+ men had increased fat mass and reduced lean mass compared to controls (%Fat in HIV+ 24.3, %Fat in controls 19.2, p=0.012; %Lean in HIV+ 72.1, %Lean in controls 77.0, p=0.014). Lean mass was lower in extremities while fat mass was higher in the trunk region in HIV+ in comparison to controls, irrespective of antiretroviral therapy. Longitudinally, patients with higher baseline %Fat (>24.2, median) presented 20% decrease in fat mass while patients with lower baseline %Fat (< or =24.2) showed a smaller, non-significant decrease in fat mass accompanied by a significant decrease (2.52%) in lean mass. Fat loss occurred in all subjects predominantly in the extremities (16.5-36.45% loss), with relative preservation of trunk fat. It is concluded that otherwise asymptomatic HIV+ men exhibit subtle body composition changes involving reduced lean mass and increased central fat mass. The pattern of weight loss over time depends on baseline fat store: patients with adequate fat stores lose predominantly fat while patients with lower baseline fat stores lose both fat and lean mass. In the entire cohort, there is a tendency towards central adiposity, with the majority of fat being lost from the extremities, a picture resembling metabolic x syndrome.

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