The Influence of −174 G/C Interleukin 6 Promoter Gene Polymorphism to Interleukin 6 Concentration in the End Stage Renal Disease Patients with Dialysis: A Single-center Experience in Indonesia

BACKGROUND: Chronic kidney disease (CKD) is classified as a multifactorial disease as a combination of genetic and environmental factors that affect the onset and progression of end-stage renal disease (ESRD). In the last decades are recognized that inflammation, where the critical modulator is cytokines, can occur before the onset of kidney disease and can be a causative factor in the development of CKD. Interleukin (IL)-6 has several polymorphisms in the promoter region, such as 174 G-C, 634 C-G, 572 G-C, and 597 G-A. G/C single nucleotide polymorphism of the IL-6 gene at position 174 in the promoter region is reported to affect the level of IL-6 expression. Unfortunately, there is a lack of data about the genotype frequencies of -174 G/C IL-6 promoter gene polymorphism in Indonesian with ESRD. AIM: This study aimed to analyze whether −174 G/C IL-6 promoter gene polymorphism influences the concentration of IL-6 in ESRD patients with dialysis in Indonesia. METHODS: We recruited 95 outpatients who were undergoing regular hemodialysis for ≥3 months at the Rasyida Renal Hospital, Medan, in this cross-sectional study. IL-6 genotype polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay method was performed to assess the quantitative IL-6 serum. RESULTS: PCR-RFLP examination showed the frequency distribution of the IL-6 genotype -174 G/C gene; 72 (75.8%) respondents had GG genotypes; 22.1% of respondents had the CG genotype, and (2.1%) had the CC genotypes. Patients with the CC genotype were statistically significant to have higher IL-6 concentration compared to other genotypes (p < 0.001). Likewise, with diabetic patients, statistics showed higher IL-6 concentration compared to non-diabetics patients (p < 0.001). CONCLUSION: This is the first study showing that -174 G/C IL-6 promoter gene polymorphism influences the IL-6 concentrations in ESRD patients with dialysis in Indonesia. Multicenter studies are needed to validate these findings

The Vascular Endothelium in Patients with Dengue Haemorrhagic Fever

BACKGROUND: Dengue fever is the most serious consequence of mosquito-borne infection worldwide. The pathophysiology of DHF in human is complex, which involve endothelial cell activation and impaired endothelial barrier leading to plasma leakage triggering the activation of the haemostatic system. The increased vascular permeability may lead to hypovolemia, hypotension and shock, which is life-threatening. AIM: The objective of the study was to determine the effects of dengue haemorrhagic fever on the vascular endothelium. METHODS: Fifty patients (males 34, females 16), were recruited, Grade 1 (n = 41), Grade 2 (n = 6), Grade 3 (n = 2) and Grade 4 (n = 1) DHF. Blood sampling was performed at the febrile, defervescence and convalescent phases for the determination of haemoglobin, haematocrit, platelets, prothrombin fragment F1 + 2, Von Willebrand Factor (VWF), vascular endothelial growth factor (VEGF) and D-dimer levels. Fifteen normal subjects were recruited to serve as normal controls. RESULTS: The patients aged between 4 and 54 years old. Grades 1 & 2 DHF showed no significant differences in the parameters studied. However, thrombocytopenia, elevated F1 + 2, VWF, VEGF and D-dimer levels were evident in febrile, defervescence and convalescent phases suggesting endothelial activation and plasma leakage. Pleural effusion was observed only in severe DHF. The three patients with Grades 3 and 4 DHF had similar study results. No mortality was recorded in the study. CONCLUSION: In dengue haemorrhagic fever, the vascular endothelium is activated, causing plasma leakage triggering the activation of the haemostatic system creating a hypercoagulable and enhanced fibrinolytic state evident by marked fibrinolysis

The Role of Placental Growth Factor, Soluble Endoglin, and Uterine Artery Diastolic Notch to Predict the Early Onset of Preeclampsia

BACKGROUND: Reducing maternal mortality is one of the targets in the Millennium Development Goals (MDGs). In a systematic review, 4.6 per cent (95% CI 2.7-8.2) of pregnancies were complicated by preeclampsia worldwide. Preeclampsia occurs in around 10% of pregnancies in the world whereas developing countries contribute more than developed countries. In developing countries, there are 13 cases of preeclampsia in every 1,000 births, whereas in developed countries only 2-3 cases of preeclampsia are found in every 10,000 deliveries. Variations in prevalence among countries reflect, at least in part, differences in the distribution of maternal age and the proportion of nulliparous pregnant women in the population. AIM: We aimed to investigate the role of placental growth factor, soluble endoglin, and uterine artery diastolic notch to predict the early onset of preeclampsia. METHODS: This study used an analytical study with a nested case-control design. The study was conducted at Bunda Thamrin Hospital, Tanjung Mulia Mitra Medika Hospital, Sundari Hospital and a private clinic, from March to November 2018 with a total sample of 70 research subjects. RESULTS: Uterine artery diastolic notch was not found in 50% of subjects. A total of 27 subjects (38.6%) had a unilateral diastolic notch, and 8 subjects (11.4%) had a bilateral diastolic notch. Cut-off point PIGF levels was 441 pg/ml, and Area Under Curve (AUC) 82.5% (95% CI 61.5%-100%), with sensitivity 80% and specificity 87.7%. The levels sEng in this study could not predict the incidence of early-onset preeclampsia (p = 0.113). Combined PlGF and pulsatile index of uterine arteries may predict early onset preeclampsia with sensitivity 40% and specificity 90.77%. From these results, pregnant women o 22-24 weeks of pregnancy, the levels of PlGF and the uterine artery pulsatility index can be a predictor of early-onset preeclampsia. Examination of PlGF levels alone is sufficient as a predictor of early-onset preeclampsia. CONCLUSION: From these results, it can be concluded that in pregnant women of 22-24 weeks, the diastolic notches in uterine arteries cannot predict the incidence of early-onset preeclampsia. PlGF levels and pulsatile index of uterine arteries can be used as predictors of early-onset preeclampsia although examination of PlGF levels alone is sufficient as a predictor of early-onset preeclampsia

The Correlation between Hemostatic Parameters and Mortality Rate in Patients with Non-Small Cell Lung Cancer

The increasing level of hemostatic parameters and tumor markers were associated with cancer progression and poor prognosis, particularly in NSCLC. The objective of this study is to determine whether there was a correlation between hemostatic parameters and mortality rate in patients with NSCLC. This was a prospective analytical study with a pretest-posttest design which included 41 patients with diagnosis of NSCLC. Plasma levels of PT, APTT, TT, D-dimer, and fibrinogen were measured before initiation of chemotherapy and remeasured after 4 cycles or 6 cycles of chemotherapy, based on the clinical condition of patients. Then, patients were followed up for 1 year to evaluate the mortality rate. The majority of subjects were male (85.4%) with adenocarcinoma (75.6%). There was no significant difference in mean between adenocarcinoma and squamous cell carcinoma (p > 0.05). Most patients died after one month of follow up (61%). The parameters which could predict high mortality rate in NSCLC were prolonged PT and the increased of D-dimer with RR > 1, although they had not significant in statistical analysis (p > 0.05). There is no correlation between hemostatic parameters and mortality rate in patients with NSCLC

Status of interleukin-6 and hepcidin levels in first-time haemodialysis patients

Background The risk of chronic kidney disease stage 5 and its progression depend on the stage and the underlying diagnosis. Haemodialysis has become the long-term maintenance therapy for these patients. The interaction among interleukin-6 (IL-6), hepcidin and the iron exporter ferroportin is a major contributor to the iron-deficiency anaemia of chronic disease. The aim of the present study was to investigate the effects of polysulphone dialyzer membrane on serum IL-6 and hepcidin, including haemoglobin levels, in first-time patients undergoing five cycles of haemodialysis. Patients and methods Totally, 11 patients (male: five, female: six) were recruited for the present study after obtaining written informed consent. Their mean age was 57.4±13.4 years, and they were undergoing haemodialysis for the first time. Hepcidin, IL-6 and haemoglobin levels were determined before the first cycle and the fifth cycle and after the fifth cycle of haemodialysis. Pearson’s correlation coefficients were also determined. Results and discussion No statistically significant differences were observed before the first cycle and after the fifth cycle of haemodialysis in haemoglobin, IL-6 and hepcidin levels nor between pre-fifth and post-fifth cycle values, except for IL-6, which showed a significant mean reduction (P=0.04) from the pre-fifth cycle of 67.0 pg/ml to a mean value of 42.9 pg/ml (64.0% reduction). Analysis of variance showed no significant variation in the parameters studied, and no significant correlations between haemoglobin and IL-6, haemoglobin and hepcidin, and IL-6 and hepcidin were found. Conclusion In this short study of five-cycle haemodialysis, significant reduction in IL-6 with no significant change in hepcidin levels was found, even though severe anaemia was present. Kidney dysfunction probably results in decreased clearance of inflammatory markers and may not be improved by haemodialysis alone. Moreover, a different approach to reduce these markers is therefore warranted

Coagulation and fibrinolysis in preeclampsia and neonates

10.1177/107602960501100415Clinical and Applied Thrombosis/Hemostasis114467-47

The humanity of war: iconic photojournalism of the battlefield, 1914–2012

This article examines the changing ethics of war photojournalism. It provides a review of the major paradigms of war communication studies, propaganda and memory studies, to argue that, despite their contributions, neither focuses on historical change in the ethics of war. In the light of an analytical discussion of iconic images of the First World War and Second World War as well as the War on Terror in terms of how they portray the battlefield the article argues that there is a historical shift towards an increasingly explicit visualisation of war, which today tends to emphasise the emotional, rather than physical, impact of the battlefield upon both soldiers and civilians. This shift, it concludes, reflects the contemporary political context of humanitarian wars fought with a view to alleviating suffering, rather than wars fought over national sovereignty