The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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The Correlation of Serum Total Testosterone, Sex Hormone Binding Globulin and Free Androgen Index with Athens Insomnia Scale Score in Polycystic Ovary Syndrome
Get PDFBACKGROUND: Polycystic ovary syndrome (PCOS), a common reproductive endocrinologic disorder in woman, was considered to be related to sleep disturbance. This study is aimed to analyze the correlation between excess androgen markers and Athens Insomnia Scale (AIS) in PCOS.METHODS: This observational, cross-sectional study of PCOS was conducted to 31 subjects to evaluate the correlation between serum total testosterone, sex hormone binding globulin (SHBG) and free androgen index with the incidence of sleep disturbance using AIS. Sleep disturbance was present if the score ≥6. The correlation between excess androgen markers and sleep disturbance was analyzed using Pearson’s coefficient of correlation or Spearman’s rho test. Correlation coefficient more than 0.5 with p6 group was higher than AIS score 0.05). No significant correlation was found between serum total testosterone, SHBG and free androgen index with AIS score. After adjusting for AIS score, there was the moderate positive correlation between serum total testosterone level although not statistically significant (r=0.54, p=0.07).CONCLUSION: The serum total testosterone level might influence the occurrence of sleep disturbance in PCOS.KEYWORDS: PCOS, androgen excess, testosterone, sleep disturbance, Athens Insomnia Scal
Phylogenetic Analysis of Human Papillomavirus 16 and 52 L1 Gene from Cervical Cancer in Bandung, Indonesia
Get PDFBACKGROUND: Chronic infection with high-risk type of human papillomavirus (HPV) can cause cervical cancer. Previous studies showed that multiple infections of HPV are found in cervical cancer caused by multiple HPV infections and the most common are HPV-16 and HPV-52. The origin of HPV-16 circulating in Indonesia varies. The purpose of this study was to explore the origin of multiple infections of HPV-52 and HPV-16 in cervical cancer by using a phylogenetic tree.METHODS: During July-November 2010, 100 women were diagnosed with cervical cancer in the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Only 96 patients were involved in this study. Ninety-six samples of HPV deoxyribonucleic acid (DNA) were isolated from biopsied tissue of cervical cancer. Multiple infections of HPV genotypes HPV-16 and HPV-52 were confirmed by using the linear assay for HPV genotyping test. Afterward,HPV-52L1 gene was amplified by using self-designed primer. L1 gene was also sequenced and analyzed using phylogenetic program (MEGA6.06).RESULTS: The result of phylogenetic tree construction showed that isolated HPV-52 originated from multiple infections of HPV-16 and HPV-52 from cervical cancer patients in Bandung were in a subgroup with isolates originating from EU077219 Canada (America) and KT799980 southwest China (Asia). Isolate HPV-16 in one subgroup with isolates originating from KU951191.1 (Southwest China).CONCLUSION: L1 gene sequence from multiple infections isolated from HPV-16 and HPV-52 from cervical cancer patients in Bandung refers to the variation of L1 gene reported from Canada and southwest China. This proves that Indonesia’s HPV clusters are located in the strains found in America and Asia.KEYWORDS: multiple infections, HPV-16, HPV-52, L1 gene, phylogeneti
CAR-T Cells: Precision Cancer Immunotherapy
Get PDFBACKGROUND: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities.CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy.SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors.KEYWORDS: chimeric antigen receptor, CAR-T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherap
Frequencies of CYP1A2 Single Nucleotide Polymorphism in Indonesian and Its Effect on Blood Pressure
Get PDFBACKGROUND: The association between caffeine with blood pressure (BP) still remains controversial. Caffeine is mainly metabolized by cytochrome-P450 (CYP)1A2 enzyme. Polymorphism of CYP1A2 is known to cause interindividual variation on enzymatic activity, thus affects caffeine metabolism and its effect on cardiovascular (CV) system.METHODS: We conducted a cross-sectional study and recruited 121 Indonesian subjects aged 25-60 years with varying coffee-drinking habits. DNA was extracted from peripheral blood and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Blood pressures were measured in the morning prior to the daily activity. Caffeine concentration in blood plasma was measured using high-performance liquid chromatography (HPLC). The differences between variables were analyzed using MannWhitney analysis and the correlations among variables were determined using multivariate logistic regression analysis.RESULTS: This study showed that the frequencies of single nucleotide polymorphisms (SNPs) among Indonesian were 31.8%, 18.2%, 25.2% and 24.8% respectively for CYP1A2*1A, CYP1A2*1B, CYP1A2*1C and CYP1A2*1F alleles. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. There were no significant differences in term of BP levels among CYP1A2 genotypes and coffee drinking habit groups.CONCLUSIONS: The frequencies of CYP1A2 SNPs in Indonesian are different with frequencies in other populations. Since the association were not statistically significant, CYP1A2 polymorphisms as the predictor of elevated blood pressuare should be investigated further.KEYWORDS: coffee, caffeine, blood pressure, single nucleotide polymorphism, CYP1A
Prospect of Natural Killer Cells in Cancer Imunotherapy
Get PDFBACKGROUND: Current understanding in molecular character of natural killer (NK) cell, its function and mechanisms, send people the ideas to develop a NK cell-based immunotherapeutic strategies against human cancer.CONTENT: Before being regards as a cell-based cellular therapy, NK cell have to be clinical proven. Early studies with NK cells infusions for acute myeloid leukemia and lung cancer showed a promising result. NK cells need simplified methods for enriching and expanding, in addition to its transfection with chimeric antigen receptors (CARs). NK-92 arise as an assuring effector cells to augment monoclonal and bispecific antibody therapy. Thus, NK cells show a potential opportunity for cell engineering, outstep the era of T cells.SUMMARY: It is believed that NK cells bring a bright hope for future cancer immunotherapies, either alone or in combination as a harmonious therapy.KEYWORDS: NK cells, NK-92 cells, immunotherapy, CA
Modulation of Caspase-3 Expression by Arcangelisia flava Post Acetaminophen-Induced Hepatotoxicity in Rat’s Liver
Get PDFBACKGROUND: Acetaminophen, when used at low doses is a safe drug, but at higher doses it induces apoptosis in hepatoma cells. Arcangelisia flava that grows widely in Kalimantan Island, Indonesia, contains berberine which is effective in protecting the liver. This work was aimed to study the effect of A. flava extract on the modulation of caspase-3 in acetaminophen-induced hepatotoxicity.METHODS: Thirty-five Wistar male rats were divided into groups: I the normal control (water); II the negative control (Arabic gum powder or PGA, 2% in suspension); III the positive control (silymarin); IV-VII (A. flava extract 100, 200, 400, and 800 mg/Kg of body weight (BW), respectively) for 14 days. At day 15th, group II-VII were induced with acetaminophen 1000 mg/Kg of BW per oral for 7 days along with the extracts. At day 22nd, the animals were measured for their serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma-glutamyl transferase (GGT), histological examination, and Western blotting.RESULTS: Acetaminophen elevated the SGOT and SGPT (3x compared to normal group), and GGT (5x compared to normal group) of the animals in group II. Pre-treatment with higher doses of A. flava extract (group VI and VII) significantly prevented the biochemical changes induced by acetaminophen. Normal histology of the liver was showed by group I, III, VII, whereas dilated sinusoids, central vein (CV) lesion, and local haemorrage were observed in group II, IV, V and VI. Western blotting showed an inhibition of caspase-3 expression by A. flava extract in dose-dependent manner.CONCLUSION: A. Higher dose A. flava extract shows hepatoprotective activity by preventing the elevation of serum transaminases and transferase levels. Eventually, no damage in the acetaminophen-induced rat’s liver was observed. This plant modulates the expression of caspase 3 protein in dose-dependent manner.KEYWORDS: Arcangelisia sp, caspase-3, berberine, hepatoprotective activity, NSAIDs, yellow roo
The Role of Ceftazidime as a Photosensitizer in Human Erythrocytes Through Oxidative Stress Mechanism
Get PDFBACKGROUND: Ceftazidime was known to cause photosensitization reactions. However, how it plays the role remained unclear. In our study, we aim to investigate the photosensitization effect of ceftazidime in erythrocytes via oxidative stress.METHODS: Samples were divided into six different groups: negative control group, positive control group and four experimental groups with 10%, 20%, 30%, and 40% ceftazidime, respectively. The positive control and experimental groups were exposed to ultraviolet (UV)-light for 2 hours. Superoxide radical, malondialdehyde (MDA), carbonyl compounds (CC) and methemoglobin (Met-Hb) levels were then measured.RESULTS: The results showed a significant increased of superoxide radical, MDA, CC and Met-Hb levels in all experimental groups compared to both negative or positive control groups (p< 0.05).CONCLUSION: In conclusion, our study confirmed the role of ceftazidime as a photosensitizer in erythrocytes via the oxidative stress mechanisms.KEYWORDS: ceftazidime, oxidative stress, photosensitizer, photosensitization
Could Complete Blood Count Parameters and Non-fasting Cholesterol Profile Describe Inflammation and Oxidative Stress in Chronic Kidney Disease?
Get PDFBACKGROUND: Establishment of inexpensive clinical laboratory tests to evaluate inflammation and oxidative stress is urgently needed in the limited resources settings. This study aims to investigate the potential of complete blood count (CBC) parameters and non-fasting cholesterol profile parameters to describe inflammation and oxidative stress in chronic kidney disease (CKD) patients.METHODS: Measurement of CBC, non-fasting cholesterol profile, high sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA) were performed in 71 CKD patients grouped into hemodialysis (HD) and non-hemodialysis (non-HD). Correlation analysis were performed to assess the potential of CBC and cholesterol profile to describe the level of hs-CRP and MDA.RESULTS: In the HD group, total cholesterol was moderately associated with hs-CRP while total cholesterol/HDL-C ratio, monocyte/HDL-C ratio, monocyte/LDL-C ratio, neutrophil/HDL-C ratio, neutrophil/LDL-C ratio, platelet/HDL-C ratio and platelet/LDL-C ratio were strongly associated with hs-CRP. In the non-HD group,only neutrophil/total cholesterol ratio and platelet/total cholesterol ratio that were associated with hs-CRP. Total cholesterol, monocyte/LDL-C ratio, neutrophil/LDL-C ratio and platelet/LDL-C ratio were moderately associated with MDA while total cholesterol/HDL-C ratio, monocyte/HDL-C ratio, neutrophil/HDL-C ratio and platelet/HDL-C ratio were strongly associated respectively with MDA in HD group. In the non-HD group, total cholesterol/HDL-C ratio, neutrophil/HDL-C ratio and platelet/HDL-C ratio were moderately associated with MDA in non-HD group while monocyte/HDL-C ratio was weakly associated with MDA.CONCLUSION: Some CBC parameters and non-fasting cholesterol profile such as cholesterol/HDL-C, monocyte/HDL-C, neutrophil/HDL-C and platelet/HDL-C ratio showed a potential to describe the inflammation and stress oxidative markers, given some strong associations with the level of hs-CRP and MDA. Further study is needed to assess whether this parameter represent long-term prognostic value among CKD patients.KEYWORDS: inflammation, oxidative stress, CRP, MDA, TAC, 8-OHdG, CBC, cholestero
The Antioxidant and Cytotoxic Effects of Cosmos caudatus Ethanolic Extract on Cervical Cancer
Get PDFBACKGROUND: Oxidative stress is closely related to all aspects of cancer. Cosmos caudatus ethanolic extract (CCEE) has been proved to have antioxidant effect that inhibited cancer cell growth due to its bioactive compounds such as catechin, quercetin and chlorogenic acid. This study aimed to evaluate antioxidant and anticancer activity of CCEE and its compounds.METHODS: Total phenol was measured according to the Folin-Ciocalteu method. Catechin, quercetin and chlorogenic acid contained in CCEE were identified by high-performance liquid chromatography (HPLC). Antioxidant activity was evaluated by 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)-reducing activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and ferric reducing antioxidant power (FRAP) activity test. The cytotoxic activity of CCEE was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on HeLa cells.RESULTS: The result showed that total phenol of CCEE was 181.64±0.93 µg Cathecin/mg extract. ABTSreducing activity test showed that catechin had the highest activity (2.90±0.04 µg/mL), while CCEE had moderate activity compared to other compounds. FRAP activity test demonstrated that catechin had the highest activity (315.83 µM Fe(II)/µg) compared to other compounds. DPPH scavenging activity of CCEE was 22.82±0.05 µg/mL. Cytotoxicity test on HeLa cell showed that CCEE had lower activity (inhibitory concentration (IC)50= 89.90±1.30 µg/mL) compared to quercetin (IC50 = 13.30±0.64 µg/ mL).CONCLUSION: CCEE has the lowest antioxidant activity compared to quercetin, catechin, and chlorogenic acid and has the lowest anticancer activity compared to quercetin. However, CCEE and its compounds has potential as antioxidant and anticancer properties.KEYWORDS: antioxidant, anticancer, catechin, Cosmos caudatus, querceti
Histomorphometric Evaluation of Allogeneic Transplantation of Bone Marrow Mesenchymal Stem Cells in Azoospermic Mice Model
Get PDFBACKGROUND: Stem cell-based therapy is one of the newest and evolving techniques in reproductive medicine. The aim of this study was to investigate the effect of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) transplantation on the testis of busulfan induced azoospermia in Balb/C mice.METHODS: Eighteen adult Balb/C mice were divided into three equal groups including control, busulfan and busulfan+cell therapy (busul+CT). For induction of azoospermia, busulfan and busul+CT groups received two injections of 10 mg/Kg of busulfan intraperitoneally with 21 days interval. In the cell therapy group 35 days after the last injection of busulfan, cluster of differentiation (CD)90+/CD34-/CD45- BM-MSCs were injected into the efferent duct of testis. Eight weeks after the BM-MSCs therapy, mice were sacrificed and tissues were taken for histological and histomorphometric evaluations.RESULTS: In busul+CT group, cellular and total diameters and cellular and cross-sectional areas significantly increased in comparison to busulfan group (p˂0.001), but there were no significant differences between busul+CT and control group (p˃0.05). Numerical density and tubular count per area unit in busul+CT and control groups were significantly less than busulfan group (p˂0.001), but there were no significant difference between busul+CT and control group (p˃0.05). The luminal diameter and area showed no significant change in all groups (p˃0.05). In busul+CT group, spermatogenesis index significantly increased when compared to busulfan and control groups (p˂0.001 and p˂0.05, respectively).CONCLUSION: Histomorphometric findings showed CD90+/CD34-/CD45- BM-MSCs transplantation on the testis of busulfan-induced azoospermic in Balb/C mice recovered spermatogenesis.KEYWORDS: mesenchymal stem cell, cell therapy, azoospermia, busulfan, mous