Uleng Bahrun

Induction of long-term lipopolysaccharide tolerance by an agonistic monoclonal antibody to the toll-like receptor 4/MD-2 complex

ABSTRACT We have established an agonistic monoclonal antibody, UT12, that induces stimulatory signals comparable to those induced by lipopolysaccharide (LPS) through Toll-like receptor 4 and MD-2. UT12 activated nuclear factor κB and induced the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in peritoneal exudative cells. In addition, mice injected with UT12 rapidly fell into endotoxin shock concomitant with the augmentation of serum TNF-α and IL-6 levels, followed by death within 12 h. On the other hand, when the mice were pretreated with a sublethal dose of UT12, the mice survived the subsequent lethal LPS challenges, with significant suppression of serum TNF-α and IL-6, indicating that UT12 induced tolerance against LPS. This effect of UT12 was maintained for at least 9 days. In contrast, the tolerance induced by LPS continued for less than 3 days. These results illuminate a novel potential therapeutic strategy for endotoxin shock by the use of monoclonal antibodies against the Toll-like receptor 4/MD-2 complex.

Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation

Stimulation of Toll-like receptor 4 (TLR4) induces not only innate but also adaptive immune responses, and has been suggested to exert adjuvant effects. Additional to such positive effects, pre-stimulation of TLR4 induces endotoxin tolerance where animals are unresponsive to subsequent lethal challenges with lipopolysaccharide (LPS). We examined the effects of pre-stimulation of TLR4 using an agonistic anti-TLR4 mAb (UT12) on antibody production in vivo. Pre-injection of UT12 prior to both primary and secondary immunization completely inhibited antigen-specific antibody responses. Cellular analysis revealed that the inhibition was not due to impairment of T-cell activation. Accordingly, T-helper activities in UT12 pre-injected mice were not impaired. In contrast, B-cell priming was defective in UT12 pre-injected mice. The observation that the expression of activation markers such as CD69 and CD86 on B cells was blocked by UT12 pre-injection supports this. Interestingly, UT12 pre-injection only showed inhibitory effects at the primary and not the secondary immunization. These results provide important information concerning the regulatory mechanisms of antibody production, especially in endotoxin-tolerant states.

BMI and Waist Circumference Have Positive Correlation With Mitochondrial DNA Copy Number in Young Adult Male

Received: February 28, 2018 Revised: April 19, 2018 Accepted: May 10, 2018 Abstract: Background: Abdominal obesity is associated with metabolic and cardiovascular diseases. Mitochondrial dysfunction is often related to metabolic disorder commonly found in abdominal obesity. Mitochondrial DNA (mtDNA) copy number is a biomarker which can be used to reflect the activity of mitochondria. Abdominal obesity is more commonly found in males compared to females and the incidence is growing in young adult male, therefore we investigated the relationship of mtDNA copy number and anthropometric and metabolic biomarkers in young adult male.

Body Mass, Total Body Fat Percentage, and Visceral Fat Level Predict Insulin Resistance Better Than Waist Circumference and Body Mass Index in Healthy Young Male Adults in Indonesia

The incidence of obesity which leads to insulin resistance (IR) and metabolic disorder is increasing in developing countries, including Indonesia. Male adults have a higher risk of abdominal obesity than females. This is associated with cardiometabolic disorders. Several anthropometric measurements have been proposed to predict IR. The aim of this study was to investigate whether body mass, body mass index (BMI), waist circumference (WC), body fat percentage (BF) or visceral fat level (VF) could become a better predictor of IR in healthy young male adults. A total of 140 healthy young male adults ranging from 18–25 years were recruited in the study. Insulin resistance was measured by calculating their Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Subjects with a HOMA-IR value ≥75th percentile, with cut off 3.75, were defined as IR. Anthropometric measurements including body weight, BMI, and WC were performed, whereas BF and VC were measured using bioelectrical impedance analysis (BIA). IR had a strong correlation with body weight, BMI, WC, BF, and VF. In the area under the curve of body mass, BF and VF were slightly greater than WC and BMI. Anthropometric measurements correlated strongly with IR but body weight, BF, VF had a stronger correlation than WC and BMI in healthy young male adults.

KETOASIDOSIS DIABETIK DI DIABETES MELITUS TIPE 1

Type 1 Diabetes Mellitus (DMT1) is an autoimmune disease characterized by impaired carbohydrate, protein and lipid metabolism resulting in insulin deficiency either absolute or relative. The absolute insulin deficiency found in DMT1, is caused by a defect in the pancreatic s cells leading to a defect in insulin synthesis by the pancreas gland. In this article, a case of type 1 DM in a child with ketoacidosis diabetes has been reported. The diagnosis was based on classical symptoms, blood glucose level, C-peptide, metabolic acidosis and keton uria. The case reported is a 12 year old girl, with main complaints of 9 kg body weight loss since three (3) years ago. The patient always felt hungry, thirsty and was frequently urinating. In her family history no such case was denied. The patient had been treated in the district general hospitals for five (5) days and was diagnosed as type 1 diabetes mellitus and was then referred to the Dr. Wahidin Sudirohusodo Hospital. The laboratory test results revealed as follows, random glucose level was 729 mg/dL, arterial blood gas analysis showed metabolic acidosis, C-peptide was 0.1 ng/mL and urinalysis showed 150 mg/dL protein, 1000 mg/dL glucose, 150 mg/ dL ketone and 250 RBC/uL. The patient was diagnosed as type 1 diabetes mellitus with diabetic ketoacidosis and received 0.5 U/kg/day insulin therapy. This case report aimed to determine the type 1 diabetes mellitus in a child is accompanied by diabetic ketoacidosis.

PNEUMATIC TUBE TERHADAP DARAH RUTIN DAN LAKTAT DEHIDROGENASE

The transportation of laboratorial samples with pneumatic tube system spends less time than when were handled by courier. Pneumatic tube system produces minor vibrations on sample due to the velocity changes during transportation and may cause changes on the blood cells and haemolysis. The aim of this study is to know the effect of sample transportation with pneumatic tube on blood cells and its effect on hemolysis. A cross sectional study was performed at Dr. Wahidin Sudirohusodo Hospital, Makassar in July 2013. Routine blood, electrolyte and LDH were tested in 12 out-patients. The researchers collected two (2) samples, for each EDTA tube (routine blood tests) and serum (electrolyte and LDH). The samples were transported using pneumatic tube and the paired samples were sent by courier. The result then were analyzed with Paired T-Test. There were no significant difference of routine blood test results between samples sent by pneumatic tube and courier except RDW. RDW were higher in samples which were sent by pneumatic tube compared to those brought by the courier (18.72±2.70% vs 17.83±2.36%, p=0.007). The electrolyte levels sent by both methods there were no significant difference, but the LDH levels were higher in samples sent by pneumatic tube (472.08±100.44 U/L vs 331.25±94.19 U/L, p=0.000). Based on this study, in common can be concluded that the pneumatic tube system does not effect on the routine blood test results, except on RDW and does not cause changes due to haemolysis (on electrolyte) except the LDH levels elevates. So based on this study, it is recommended to send samples for LDH test only by courier.

CORRELATION OF ANTINUCLEAR ANTIBODY (ANA) PROFILE WITH HEMATOLOGIC AND RENAL DISORDERS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic Lupus Erythematosus (SLE) adalah penyakit autoimun dan bersifat multi organ. Kelainan hematologi sering ditemukan di penyakit ini, begitu juga dengan kelainan ginjal yang merupakan salah satu faktor yang sangat berpengaruh. Uji ANA profile dapat mengetahui subtipe antibodi antinuklear yang khas. Autoantibodi tersebut diduga berhubungan dengan manifestasi klinis. Penelitian ini merupakan penelitian analitik retrospektif di Laboratorium Patologi Klinik dan Instalasi Rekam Medik RSUP. Dr. Wahidin Sudirohusodo Makassar dengan mengambil data hasil ANA profile, darah rutin dan urinalisis pasien terduga SLE masa waktu Januari 2014–Juli 2016. Data dikelompokkan menjadi SLE dan nonSLE. Analisis statitik dengan uji Chi Kuadrat dan Fisher. Dari 72 sampel, 39 dengan diagnosa akhir SLE. Terdapat hubungan bermakna antara anti RNP/Sm, Sm, SS-A, Ro-52, dsDNA, Nucleosome, Histone, Ribosomal P dengan SLE (p<0,05). Terdapat hubungan bermakna antara anti dsDNA (p=0,029) dan anti nucleosome (p=0,037) dengan anemia serta anti dsDNA (p=0,013) dan anti nucleosome (p=0,036) dengan gangguan ginjal. Tidak ditemukan hubungan bermakna antara autoantibodi dalam penelitian ini dengan leukopenia, limfopenia dan trombositopenia. Anti RNP/Sm, Sm, SS-A, Ro-52, dsDNA, nucleosome, Histones, Ribosomal P berhubungan dengan SLE. Anti dsDNA dan anti nucleosome berhubungan dengan anemia dan gangguan ginjal pada SLE, sehingga mungkin dapat digunakan untuk meramalkan kejadian tersebut, walaupun dibutuhkan penelitian lanjutan untuk membuktikannya. Tidak ditemukan autoantibodi yang dapat dihubungkan dengan leukopenia, limfopenia dan trombositopenia.

PLATELET-LYMPHOCYTE RATIO (PLR) MARKERS IN ACUTE CORONARY SYNDROME (Platelet Lymphocyte Ratio (PLR) sebagai Petanda Sindrom Koroner Akut)

Sindrom Koroner Akut (SKA) merupakan puncak manifestasi klinis aterosklerosis di arteri koroner. Inflamasi terjadi dari tahap awal pembentukan ateroma sampai ruptur plak dan trombosis. Trombosis memainkan peran penting dalam perjalanan penyakit SKA. Trombositosis dan limfopenia berhubungan dengan derajat inflamasi sistemik dan Rasio Platelet Limfosit (PLR) menjadi petanda baru yang melibatkan kedua tolok ukur hematologi tersebut. Penelitian ini merupakan penelitian retrospektif di Rumah sakit Dr. Wahidin Sudirohusodo Makassar dengan mengambil data pasien SKA UAP, STEMI, NSTEMI dan menilai PLR dari pemeriksaan darah rutin saat masuk Rumah sakit. Data PLR dibandingkan berdasarkan jenis SKA, kemudian dibandingkan dengan kontrol sehat. Hasil penelitian didapatkan 223 data pasien SKA UAP, STEMI dan NSTEMI masing-masing 89, 68, 66 data dan kontrol normal 198 data. Hasil uji statistik Kruskal wallis menunjukkan perbedaan bermakna PLR antara pasien UAP, NSTEMI dan STEMI (p=0,011). Hasil uji post hoc menunjukkan perbedaan bermakna antara UAP dan NSTEMI (p=0,023), UAP dan STEMI (p=0,006), tetapi tidak berbeda bermakna antara NSTEMI dan STEMI (p=0,827). Nilai PLR pasien SKA lebih tinggi dibandingkan dengan pembanding (p=0,037). Berdasarkan hasil penelitian didapatkan nilai PLR meningkat di SKA dibandingkan dengan kontrol normal. Nilai PLR di STEMI dan NSTEMI lebih tinggi dibandingkan UAP, kemungkinan berhubungan dengan pembentukan trombus dan infark miokard.

ANGKA BANDING NETROFIL/LIMFOSIT DI POPULASI DEWASA MUDA

Previous studies have shown that neutrophil/lymphocyte ratio in bacteremia is higher than nonbacteremia, therefore it could be used as a marker to distinguish both conditions in patients with sepsis .Another study on oncology patients in ICU showed a correlation between the severity of clinical course and the increase of neutrophil/lymphocyte ratio. In physiological condition, neutrophil/lymphocyte ratio 6. Neutrophil/lymphocyte ratio is a sensitive, fast, cost effective and applicable laboratory test for routine use, therefore this test result can be used as the parameter to assess clinical condition of patients. However, a reference value of neutrophil/lymphocyte ratio has never been defined, especially in Makassar City, South Sulawesi Province. The aim of this study was to know the neutrophil/lymphocyte ratio in a healthy young adult population. A cross sectional study was conducted from March to April 2014, involving residents (specialistic candidates in Medical Faculty, Hasanuddin University, who underwwent medical checkup and voluntarily joined this study. Samples consisted of 198 persons who fulfilled the inclusion criteria with an age range between 24-40 years old, comprising 84 males (42.42%) and 114 females (57.58%). The neutrophil/lymphocyte ratio for all samples was 1.95 (1.15-4.74). Mann Whitney test showed that there was no significant difference of neutrophil/lymphocyte ratio between males and females, 1.88 (1.25-4.74) vs 1.95 (1.15-4.12), p=0.65 and neither between the age group 21-30 years old and 31-40 years old, 1.95 (1.21-4.74) vs 1.94 (1.15-4.09), p=0.82.

LDL TEROKSIDASI DAN KEPADATAN MINERAL TULANG

Osteoporosis is defined by low bone density and micro architectural deterioration of bone tissue with a consequent increase in bone fragility and risk of fracture. Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis, which need special device, and expensive fee. So it is not routinely done, therefore another type of examination methods is needed. Oxidized LDL (oxLDL) cholesterol is the parameter correlated with diminished bone mineral density by affecting osteoblast and osteoclast. The aim of this study was to know the role of oxLDL in diminished bone mineral density by analyzing it. Cross sectional study was held on 78 subjects during the period of October 2011 until June 2013 using the primary data from 30−60 years women population in Makassar, whose FPG, ALT, AST, urea and creatinine are within normal limit. Using oxLDL 6.8mU/L value as cut off, had found odds ratio increase 2.2 times with 68.8% probability to suffer diminished BMD. Receiver Operating Characteristic (ROC) analysis show area under curve is 60.8%, using 8.05mU/L as a cut off point resulting 68.8% sensitivity, 59.2% specifity, 76.1% positive predictive value, 50% negative predictive value, 1.71 positive likelihood ratio, 0.53 negative likelihood ratio and 65.4% accuracy. Concluded that oxLDL ≥6.8mU/L increases risk to suffer diminished BMD 2.2 times. As a diagnostic marker, oxLDL has a weak diagnostic strength and accuracy (68.8% sensitivity and 59.2% specifity). The researchers have the opinion to perform a further study with larger and various population, concern on oxLDL bio availability and use it with another parameter as a panel test.