The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Early Screening of Hemoglobinopathy in Indonesia Using Erythrocyte Indices
Get PDFBACKGROUND: The mutation spectrums of hemoglobinopathy are different among populations that yield a different result of erythrocyte indices. Calculation of erythrocyte indices with some formula has been reported to differentiate between hemoglobinopathy and non-hemoglobinopathy, but its cut-off should be recalculated specific for each population to gain a better sensitivity and specificity. We aimed to evaluate red blood cell count (RBC), Mentzer index, red cell distribution width (RDW), RDW index (RDWI), Shine and Lal index (S&L) and Green and King index (G&K) to screen hemoglobinopathy in Indonesia.METHODS: A retrospective cross-sectional study was performed on 202 subjects. The diagnosis of hemoglobinopathy was determined based on the results of complete blood count (CBC) data, high-performance liquid chromatography (HPLC) and Hemoglobin H (HbH) inclusion body. The ferritin concentration was checked to determine the status of iron. The erythrocytes indices were analyzed and calculated to predict hemoglobinopathy. RESULTS: A total 202 subjects who met the criteria were involved in this study. Fifty percent showed pure hemoglobinopathy and 4% showed a combination of thalassemia and hemoglobinopathy. The hemoglobin concentration and RBC were significantly higher, and the mean corpuscular volume (MCV) and RDW were significantly lower in hemoglobinopathy compared to iron deficiency. The difference was not significant if the hemoglobinopathy was combined with iron deficiency. By this study's cut-off, the G&K and RDWI showed the highest accuracy, sensitivity, and specificity.CONCLUSION: The new cut-off of erythrocyte index and its calculation to screen hemoglobinopathy in Indonesia showed a higher sensitivity and specificity, especially for G&K and RDWI with cut-off 73 and 228, respectively. The presence of iron deficiency in hemoglobinopathy could decrease the sensitivity.KEYWORDS: hemoglobinopathy, RBC, Mentzer index, RDW, RDWI, S&L, G&
The Immunobiology of Cancer: An Update Review
Get PDFBACKGROUND: The introduction of mechanism based targeted therapies to treat human cancers has been pledge as one of the results of three decades of remarkable progress of research into the mechanisms of cancer pathogenesis. We ponder how the description of hallmark principles is start to inform therapeutic development currently and may increasingly do so in the future.CONTENT: There are 10 biological capabilities involved as the hallmarks of cancer, during the multistep of human tumors development. These hallmarks simplify the complexities of neoplastic disease into a structured rational principles, includes sustaining proliferative signaling, eluding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genome instability, inflammation, reprogramming energy metabolism and evading immune destruction.SUMMARY: The 10 hallmarks of cancer, in other words, the tumor’s distinctive and complementary capabilities that enable its growth and metastatic dissemination, continue to provide a solid foundation for understanding the biology of cancer. The acknowledgment of the widespread applicability of these concepts will increasingly influence the development of new manners to treat human cancer.KEYWORDS: hallmark of cancer, cancer genome, inflammation, cancer immunology, metastasi
The Effect of Polysaccharides Peptides Ganoderma Lucidum to Aortic Foam Cell Count and Lipid Profile in Type 2 Diabetic Model Rattus Norvegicus Strain Wistar
Get PDFBACKGROUND: Type 2 Diabetes Mellitus (DM) is one of dominant factors in cardiovascular deaths and induces endothelial dysfunction. A definite sign of endothelial dysfunction is foam cells formation derived from oxidized LDL. This study was conducted to determine effect of Polysaccharides Peptides (PsP) Ganoderma lucidum to foam cell counts and lipid profile in diabetic model rats with high-fat diet.METHODS: Treatment group was categorized to negative control, positive control, DM-50, DM-150, and DM-300. Type 2 DM induced by Streptozotocin. PsP is administered with predetermined doses on each treatment’s group (50, 150, and 300 mg/kgBW) for 12 weeks. Measurements of foam cell count were held after obtaining rat’s aorta. To assess lipid profile, blood sample was taken from the rat's heart. Data analyzed by One-way ANOVA and Post Hoc Tukey tests.RESULTS: The administration of Ganoderma lucidum PsP to diabetic model rats provided a significant difference in lowering foam cell (p=0.017; CI 95%). It also gave significant difference between levels of each lipid components (Total Cholesterol, Trygliceride, LDL and HDL) in at least two treatment groups (p=0.010; CI 95%). Based on Post Hoc Tukey tests, the relationship between administration of PsP and foam cell is significant (p=0.002).CONCLUSION: PsP has antioxidant and anti-inflammatory effect in type 2 DM model Rattus norvegicus strain wistar, which can inhibit atherosclerosis and endothelial damage process. Further studies are necessary to evaluate the benefits of PsP as an adjuvant therapy in management of diabetic dyslipidemia.KEYWORDS: PsP, Ganoderma lucidum, foam cell, lipid profile, D
Growth and Osteogenic Differentiation of CD117+ Dental Pulp and Periodontal Ligament Cells
Get PDFBACKGROUND: Dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) have been suggested as valuable seed cells for bone engineering, suggesting that both stem cells are potential osteogenic sources. Since DPSC and PDLSC seem like to have similar potential in bone formation, we conducted a study to compare morphology, immunophenotype and cell growth of DPSC and PDLSC isolated from the same teeth.METHODS: Human dental pulps and periodontal ligaments were obtained from freshly extracted partial impacted third molar teeth. Collected samples were digested with type I collagenase. Resulted cell suspension was washed and cultured. For biomarker identification, the cells were fixed and bound with anti-fluorescein isothiocyanate (FITC)-cluster of differentiation (CD)117 antibody. For cell growth quantification, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used. Meanwhile for osteogenic differentiation, the cells were cultured in osteogenic medium for 1-3 weeks, fixed and stained with alizarin red.RESULTS: Morphology of dental pulps cell (DPC) and periodontal ligament cell (PDLC) in passage 5 was similar. Clear CD117 green fluorescence of DPC and PDLC in passage 5 was observed. Cell growth rate of PDLC was higher than the one of DPC, 0.3858 and 0.3848 respectively. DPC formed bone nodule on the third week culture in osteogenic medium, while PDLC showed bone nodule formation on the second week culture.CONCLUSION: We suggest that DPC and PDLC are potential seed cells for osteogenic regeneration, since they had cell growth capacity and osteogenic differentiation, particularly PDLC that had faster osteogenic differentiation.KEYWORDS: dental pulp, periodontal ligament, cell, growth, osteogenic differentiatio
Telomeres and Telomerase in The Aging Heart
Get PDFBACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease.CONTENT: Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a and PGC-1b in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging.SUMMARY: The aging myocardium with telomere shortening and accumulation of senescent cells restricts the tissue regenerative ability, which contributes to systolic or diastolic heart failure. Moreover, patients with ion-channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments.KEYWORDS: aging, telomere, telomerase, aging heart, mitochondria, cardiac stem cel
Busulfan Treatment Effects on Testicular Tissue and Serum Levels of Anti- Mullerian Hormone and Testosterone in Adult Mice
Get PDFBACKGROUND: Busulfan, a chemotherapeutic drug, is an alkylating antineoplastic agent that belongs to the class of alkyl sulfonates and has some side effects on fertility. This research was aimed to investigate the effects of busulfan on testicular tissue and serum levels of anti-Mullerian hormone (AMH) and testosterone in adult mice.METHODS: Eighteen adult male Balb/C mice were collected randomly and were assigned in three groups including; control, azoospermia and spontaneous recovery. The groups, except for control group, received two injections of busulfan (10 mg/kg) intraperitoneally with 21-days interval in order to induce azoospermia. Thirty-five and 140 days after the last injection, the effects of busulfan on testicular tissue were evaluated by histologic, histomorphometric and hormonal changes. AMH and testosterone were measured by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) kits, respectively.RESULTS: Hormonal analyses showed no significant differences in AMH and testosterone serum levels. Histologic and histomorphometric evaluation showed disrupted spermatogenesis in azoospermia group, and restoration of spermatogenesis spontaneously in spontaneous recovery group.CONCLUSION: Busulfan at doses was used had no effect on AMH and testosterone serum levels. Busulfan can also induce azoospermia on a temporary basis however, in long term, spontaneous recovery can occur. The results indicated that some side effects are reversible and may depend on the dose applied.KEYWORDS: Busulfan, anti-Mullerian hormone, testosterone, mouse, testi
DNA Sequence Analysis of dtxR Gene (Partial) of Corynebacterium diphtheriae Causing Diphtheria in Jawa and Kalimantan Islands, Indonesia
Get PDFBACKGROUND: dtxR gene is a global regulator that can be used as a marker for detection of Corynebacterium diphtheriae (C. diphtheriae) and it is also a representative tool for mapping purpose (molecular typing) of this bacteria. The aim of this study was to analyze the DNA sequences of partial dtxR gene of C. diphtheriae causing diphtheria in some region of Indonesia. DNA sequence analysis was used to verify the accuracy of the in-house multiplex polymerase chain reaction (PCR) method that used for detection of C. diphtheriae in the clinical specimen as well as a preliminary study to determine the strain diversity of C. diphtheriae circulating in Indonesia.METHODS:Ten PCR products targeting the dtxR gene that have been detected as positive C. diphtheriae previously by in-house multiplex PCR used as samples in this study. The DNA sequencing carried out by Sanger method and the sequence data was analyzed by Bioedit software offline and basic local alignment sequence typing (BLAST) online.RESULTS: All of DNA sequence analyzed in this study were similar or identical to the dtxR gene sequence data of C. diphtheriae registered in GenBank. Within the 162 nucleotides (base 150-311) of dtxR gene that analyzed, at least 2 clonals were found among 10 samples. Substitutions of 2 nucleotides (base 225 and 273) was detected, both were silent mutation.CONCLUSION:Ten partial DNA sequences of dtxR genes in this study verify the accuracy of in-house multiplex PCR which used to identify the bacteria causing diphtheria in the clinical specimen. The DNA sequences also represent the existing diversity of the bacteria causing diphtheria circulating in Indonesia.KEYWORDS: dtxR, C. diphtheriae, diphtheria, Indonesi
Telomere in Aging and Age-Related Diseases
Get PDFBACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span.CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases’ pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications.SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management.KEYWORDS: telomerase, cellular senescence, aging, cance
Differences in the Effect of Using Sterile Water for Irrigation and Normal Saline Washing to Peritoneal Adhesion Post-Laparotomy on White Rats
Get PDFBACKGROUND: Peritoneal adhesion is a side effect of abdominal surgery that often occurs. Many efforts were made in abdominal surgery to prevent or minimize the occurrence of this adhesion. One way to reduce the risk of bowel adhesions is through washing peritoneum method, so the differences in the use of washing solution on the incidence of adhesions after laparotomy surgery need to be investigated. The objective of this study is to determine differences in the effect of using sterile water and normal saline for washing irrigation to peritoneal adhesions after laparotomy in white rats.METHODS: This was an experimental study. Thirty-two sample of white rats were divided into two groups, group A and Group B, each group consists of 16 rats. Group A got washing using normal saline and group B got washing using sterile water for irrigation in laparotomy procedure to assess the peritoneal adhesion microscopically after relaparotomy. RESULTS: This study was conducted in April-May 2016. The founding of peritoneal adhesion after laparotomy in white rats using sterile water for irrigation in grade 1 were seven samples, grade 2 were five samples and grade 3 were four samples. Meanwhile, the founding of peritoneum adhesion after laparotomy using normal saline grade 1 are two samples, grade 2 are five samples, and grade 3 are nine samples. Statistically, significant differences were found (p<0.05).CONCLUSION: Some risk factors can lead to adhesion, such as trauma surgery, tissue ischemia, infection blood and foreign body irritating. Intraperitoneal irrigation with sterile water for irrigation is better than the use of normal saline in preventing peritoneal adhesion.KEYWORDS: peritoneal adhesions, sterile water for irrigation, normal salin
The Blockade of Glutamate N-methyl-D-aspartate Receptors into the Prelimbic of Prefrontal Cortex Decreases Morphine-induced Conditioned Place Preference in Rat
Get PDFBACKGROUND: The prelimbic area (PL) of the prefrontal cortex is susceptible to abnormal developmental stimuli that raises the risk of addiction. Glutamate receptors play a key role in opiate reinforcement and reward functions in this area. Therefore, we examined the effect of the DL-2-amino-5-phosphonopentanoic acid (AP5), as N-methyl-D-aspartate (NMDA) receptor antagonist into the PL on the phases of conditioned place preference (CPP) induced by morphine.METHODS: Male Wistar rats were divided into 12 groups (3 surgical groups for each dose of morphine in any phase of CPP) and anaesthetized with chloral hydrate. Cannula was implanted into the PL and the AP5 was injected into this area and morphine-induced CPP was investigated. Data were processed with the commercially available SPSS 22 software using one-way ANOVA and Tukey's test. p<0.05 were considered statistically significant.RESULTS: Our findings indicated, morphine in doses of 2.5 to 10 mg/kg induced CPP. Microinjection of various doses of the AP5 into the PL before the administration of the effective dose of morphine significantly reduced place preference in the acquisition and the expression phases of the CPP test compared to the sham group (p<0.001). In another set of our experiments was seen that, different doses of the AP5 with the ineffective dose of morphine only reduced the expression phase of the CPP (p<0.001) while, produced neither preference nor aversion effect on the acquisition phase (p=0.147).CONCLUSION: It seems that the glutamate NMDA receptors in the PL through memory formation and morphine-related reward signals play a critical role in addiction process during morphine-induced CPP.KEYWORDS: N-methyl-aspartate, morphine, glutamate receptor, prefrontal cortex, rewar