The Indonesian Biomedical Journal

32-9

Authors: A Guntur Hermawan

Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS). In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP), despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO). The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome.

45-52

Authors: Ampi Retnowarnadi, Siti Boedina Kresno, Mansyur Arif

BACKGROUND: Breast cancer is the most frequent cancer diagnosed among women. Many factors influence the carcinogenesis of breast cancer. The aim of this study to analyze the role of obesity (waist circumference and body mass index), serum Estradiol levels, TNF-α, and Adiponectin in the occurrence of breast cancer. METHODS: This was observational study with casecontrol design. Eleven breast cancer patients as cases and twelve FAM (Fibroadenoma Mammae) patients as controls were analyzed. The serum Estrogen, TNF-α and Adiponectin were examined in their association with breast cancer risk. RESULTS: Women with breast tumor and waist circumference > 80 cm have significantly higher breast cancer risk than women with breast tumor and waist circumference < 80 cm (OR 8,75; 95% CI : 1,24 – 61,88; p= 0,029). Women with breast tumor and higher serum TNF-α levels ( > 2,30 pg/ml) have higher breast cancer risk (19,25 times) than women with breast tumor and have lower serum TNF-α levels (95% CI : 1,77 - 209,55, p = 0,015). Whereas, women with breast tumor and lower Adiponectin/TNF-α ratio (< 2,13) have higher breast cancer risk (22,5 times) than women with breast tumor and higher Adiponectin/TNF-α (95% CI: 2,60 – 194,51; p = 0,005). CONCLUSION: These results suggest that high concentration of serum TNF-α, waist circumference > 80 cm and low Adiponectin/TNF-α ratio in women with breast tumor are significantly associated with an increased risk for breast cancer.

61-7

Authors: Anwar Santoso, Sri Wardani, Ketut Surayana

BACKGROUND: Neopterin is a soluble biomarker of monocyte activation and its increased concentration might be expressed in atherosclerosis. Until recently, there has been lacking of information on the prognostic role of neopterin in acute coronary syndromes (ACS). The study was aimed at measuring the associations between elevated serum neopterin and increased risk of cardiovascular (CV) events in ACS. METHODS: This was a prospective cohort study, recruited 71 ACS patients from January 31 through August 31, 2007 in Sanglah Hospital of Udayana School of Medicine, Denpasar – Bali. Cardiovascular events, such as: CV death, recurrent myocardial infarction, stroke and recurrent myocardial ischemia were previously defined. Relative risk and survival rate were measured successively by Cox proportional model and Kaplan-Meier curve. RESULTS: Of 71 ACS patients aged 56.8 ± 9.5 years, 21 (29.5%) subjects underwent CV events. Overall mean followup was 151.6 (95% CI: 129.7 – 173.5) days. Baseline characteristic were similarly distributed between groups with the highest quartile neopterin level (≥ 14.7 nmol/L) than those with lowest quartile (≤ 6.2 nmol/L). Patients with the highest quartile had the worst survival curve than those with the lowest quartile (log-rank test; P = 0.047). On Cox proportional model, relative risk of highest quartile group was 5.84 (95% CI: 1.19 – 28.47; P = 0.029) compared to lowest quartile, after being adjusted with other predictors. CONCLUSIONS: Elevated serum neopterin is associated with increased risk of CV events in acute coronary syndromes.

73-9

Authors: Dewi Muliaty, Irawan Yusuf, A Guntur Hermawan

BACKGROUND: Biochemical markers may be used in diagnosis, prognostic and monitoring treatment and therapy for sepsis patients. In this study we used Lipopolysacharide Binding Protein (LBP), serum-Intercellular Adhesion Molecule-1 (ICAM-1), Procalcitonin (PCT) and protein C activity. LBP is related to lipopolysachharide or gram-negative bacterial endotoxin which bound to LBP and induced inflammatory response. ICAM-1 is associated with endothelial dysfunction in response to systemic inflammatory and septic condition. PCT increased in bacterial infection and in severe systemic inflammatory. Role of Protein C is protecting the intravascular system to systemic inflammation, sepsis and the concomitant intravascular coagulopathy. The aim of this study was to examine the associations between levels of serum LBP, sICAM-1, PCT, and protein C activity with the clinical outcome of SIRS or sepsis patients. METHODS: We included 19 post surgery patients with SIRS criteria from intensive care unit (ICU) and evaluated the level of LBP serum with Chemiliuminescent Enzyme Immunoassay (Diagnostic Product Co.), ICAM-1 with ELISA (R&D System), PCT with immunochromatography (BRAHMS), protein C activity with chromogenic method (Dade Behring). We performed the samples serially at the first admission of patients and after 72 hours. Data were analysed by non-parametric with Wilcoxon test and Mann-Whitney test. Correlation study between biomarkers calculated by Kendall’s tau and Spearman’s rho. RESULTS: Of 19 patients, 9 (47,4%) died and 10 (52,6%) surviving. The level of LBP serum decreased after 72 hours in surviving-sepsis patients, and increased in nonsurviving sepsis patients with significant different levels at 72 hours examination (P<0.05). The level of soluble-ICAM-1 which was high in the first admission showed in non-surviving sepsis patients, but the difference levels was not significant between surviving and non-surviving patients (P>0.05). In all patients were found high level of PCT serum since the first admission examination, decreasing levels were occurred significantly in surviving patients after 72 hours (P<0.05) where high PCT levels were found in non-surviving patients after 72 hours. The median level of plasma protein C activity was low at the first admission especially in non-surviving sepsis patients, the decreasing level was not significantly different after 72 hours (P>0.05) both in surviving and non-surviving patients. CONCLUSIONS: Increasing level of LBP and PCT in sepsis patients showed that those biomarkers useful for predict the clinical outcome in sepsis patients. Decreasing protein C activity level was not a good predictor in worsening clinical outcomes. Soluble ICAM-1 level was not a good marker for predict risk of sepsis severity. LBP and PCT tests were more useful in serially testing from the first admission of sepsis patients, those tests are more faster than bacterial culture.