GANGGUAN BERJALAN PADA KRETIN ENDEMIK

A study of 27 cases of cretinism is hereby reported. A prominent feature of the disease is a disturbance in coordination, which manifests itself as delayed and difficulty in walking. The symptoms will become more complex, the earlier the deficiency in iodine and thyroid hormone exists

Nephroprotective Effect of Pentoxyphylline Through Improvement in the Expression of TGF-beta1, Collagen Type-1, and Renal Interstitial Fibrosis in Swiss Strain Mice After Being Induced by Doxorubicin

BACKGROUND: Use of doxorubicin (DXR) in the treatment of cancer has been increasing along with the increase in cancer morbidity. Nephrotoxic effects of DXR are still a problem. Pentoxyphylline (PTX) as an electron-donor material can be nephroprotective, so the combination of DXR and PTX might reduce the nephrotoxic effects of DXR. The aim of this study was to prove the nephroprotective effect of PTX and DXR nephrotoxicity through the improvement of TGF-β1, collage type-1, and renal interstitial fibrosis. METHODS: Twenty-four males Swiss strain mice, divided into three groups namely Control (C) injected with NaCl 0.9%; DXR induced nephrotoxicity (D); and effect of PTX on D (P/D) by intraperitoneally, respectively, each group consisted of 8 mice. Injections were given once a week for three consecutive weeks. At 8th week post-treatment, all eight mice of each group were sacrificed. Examination of TGF-β1 and collagen type-I expression was done by immunohistochemistry with monoclonal antibody. Renal interstitial fibrosis examination was done by a histopathologist, using Verheoff van Giesen staining. The statistic analysis was carried out using one-way ANOVA. RESULTS: TGF-β1 expression increased from C to D and subsequently decreased in P/D (4.50±3.89 vs. 177.88±68.78 vs. 36.88±9.51). Collagen type-I expression increased from C to D and subsequently decreased in P/D (12.00±14.32 vs. 186.25±125.62 vs. 36.00±29.14). Renal interstitial fibrosis expression increased from C to D and subsequently decreased in P/D (16.75±6.14 vs. 85.00±7.33 vs. 60.50±11.40). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were higher significantly in D group as compared to C group (p<0,001). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were lower significantly in P/D group as compared to D group (p<0.005). CONCLUSIONS: PTX was proved to be nephroprotector inducing by DXR. KEYWORDS: PTX, nephroprotector, TGF-β1, collagen type-I, renal interstitial fibrosis

Development of Immunopathobiogenesis on SIRS-Sepsis

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.KEYWORDS: sepsis, innate immunity, adaptiv

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Nephroprotective Effect of Pentoxyphylline Through Improvement in the Expression of TGF-beta1, Collagen Type-1, and Renal Interstitial Fibrosis in Swiss Strain Mice After Being Induced by Doxorubicin

BACKGROUND: Use of doxorubicin (DXR) in the treatment of cancer has been increasing along with the increase in cancer morbidity. Nephrotoxic effects of DXR are still a problem. Pentoxyphylline (PTX) as an electron-donor material can be nephroprotective, so the combination of DXR and PTX might reduce the nephrotoxic effects of DXR. The aim of this study was to prove the nephroprotective effect of PTX and DXR nephrotoxicity through the improvement of TGF-β1, collage type-1, and renal interstitial fibrosis.METHODS: Twenty-four males Swiss strain mice, divided into three groups namely Control (C) injected with NaCl 0.9%; DXR induced nephrotoxicity (D); and effect of PTX on D (P/D) by intraperitoneally, respectively, each group consisted of 8 mice. Injections were given once a week for three consecutive weeks. At 8th week post-treatment, all eight mice of each group were sacrificed. Examination of TGF-β1 and collagen type-I expression was done by immunohistochemistry with monoclonal antibody. Renal interstitial fibrosis examination was done by a histopathologist, using Verheoff van Giesen staining. The statistic analysis was carried out using one-way ANOVA.RESULTS: TGF-β1 expression increased from C to D and subsequently decreased in P/D (4.50±3.89 vs. 177.88±68.78 vs. 36.88±9.51). Collagen type-I expression increased from C to D and subsequently decreased in P/D (12.00±14.32 vs. 186.25±125.62 vs. 36.00±29.14). Renal interstitial fibrosis expression increased from C to D and subsequently decreased in P/D (16.75±6.14 vs. 85.00±7.33 vs. 60.50±11.40). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were higher significantly in D group as compared to C group (p<0,001). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were lower significantly in P/D group as compared to D group (p<0.005).CONCLUSIONS: PTX was proved to be nephroprotector inducing by DXR.KEYWORDS: PTX, nephroprotector, TGF-β1, collagen type-I, renal interstitial fibrosi

Lipopolysaccharide Binding Protein, Soluble-Intercellular Adhesion Molecule-1, Procalcitonin, and Protein C Activity and Clinical Outcome in Systemic Inflammatory Response Syndrome (SIRS) or Sepsis Patients

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&amp;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 (p0.05). 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 (p0.05) 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. KEYWORDS: sepsis, SIRS, lipopolysaccharide binding protein, soluble intercellular adhesion molecule-1, procalcitonin, protein