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Background and Objective: Premature ventricular complex (PVC) burden exhibits one of three circadian types, classified as fast-type, slow-type, and independent-type PVC. It is unknown whether PVC circadian types have different heart rate variability (HRV) parameter values. Therefore, this study aimed to evaluate differences in HRV circadian rhythm among fast-, slow-, and independent-type PVC., Methods: This cross-sectional observational study consecutively recruited 65 idiopathic PVC subjects (23 fast-, 20 slow-, and 22 independent-type) as well as five control subjects. Each subject underwent a 24-hour Holter to examine PVC burden and HRV. HRV analysis included components that primarily reflect global, parasympathetic, and sympathetic activities. Repeated measures analysis of variance was used to compare differences in HRV circadian rhythm by PVC type., Results: The average PVC burden was 15.7%, 8.4%, and 13.6% in fast-, slow-, and independent-type idiopathic PVC subjects, respectively. Global, parasympathetic nervous system, and sympathetic nervous system HRV parameters were significantly lower in independent-type PVC versus fast- and slow-type PVC throughout the day and night. Furthermore, we unexpectedly found that tendency towards sympathetic activity dominance during nighttime was only in independent-type PVC., Conclusion: The HRV parameters are reduced in patients with independent-type PVC compared to fast- and slow-type PVC. Future research is warranted to determine possible differences in the prognosis between the three PVC types., Competing Interests: All authors declared no conflicts of interest., (© 2025 Acta Medica Philippina.)

Objective: The objective of this study was to investigate the effectiveness and safety of seahorse (Hippocampus comes L.) extract on hematological profile and body weight on rats induced by depo medroxyprogesterone acetate (DMPA)., Materials and Methods: Thirty adult male Sprague-Dawley rats with 200-250 gm and 8 weeks old. All rats were intramuscularly administered 1.25 mg/kg BW DMPA Merck Depo Geston at 150 mg/3 ml. The animals were divided into five main groups (6 each), consisting of aquadest (G1), CMC 1% (G2), seahorse extract (SE) dose 150 mg/kg BW (G3), 225 mg/kg BW (G4), and 300 mg/kg BW (G5). All rats were weighed until the end of the treatment week., Results: The hematological profile and body weight of the group given SE tended to increase compared to the group not given extract; however, our hematological profile and body weight were in the normal range for rats., Conclusion: We find that SE enhances the effectiveness of the hematological profile, body weight, and safety of rats induced by DMPA., Competing Interests: No competing interests were disclosed., (© The authors.)

The use of skin barrier-enhancing topical medication is a favorable approach for the treatment of occupational hand dermatitis (OHD). Cocos nucifera or coconut oil is one of the best sources of lipid enriched with laurate acid, and glycerin is a well-known humectant that improves skin hydration. This study is aimed is to evaluate the effectiveness of C. nucifera and glycerin for secondary prevention of OHD among batik (Indonesian traditional fabric) workers. In a randomized, double-blind, crossover trial, the effect of glycerine-C. nucifera cream versus glycerin-only was considered with multiple afterwork applications of moisturizer over a 2-week period on batik workers with OHD. Assessment of trans-epidermal water loss (TEWL), skin capacitance, and a clinical assessment using the Hand Eczema Severity Index (HECSI) were carried out at day 0 and 14. The results show thirty-two batik dyeing and/or rinsing workers were enrolled in the study with mild to moderate OHD. Clinical improvement was demonstrated by 20% decrease in HECSI and TEWL, and 20% increase in skin capacitance. Both moisturizers were equally effective for the secondary prevention of OHD. As a conclusion, glycerine-C. nucifera and glycerin-only cream are equally effective for secondary prevention for OHD among batik worker to reduce the prevalence of hand dermatitis., (© 2024. The Author(s).)

Objectives: Occupational pesticide exposure, chlorpyrifos (CPF) in particular, may adversely affect the thyroid. The purpose of this study was to evaluate the determinants of thyroid function as indicated by the serum concentration of thyroid-stimulating hormone (TSH) among Indonesian vegetable farmers with primary exposure to CPF., Methods: A total of 151 vegetable farmers participated in this study. The sociodemographic and occupational characteristics of the participants were obtained using a structured interviewer-administered questionnaire. A validated quantitative method was used to estimate the cumulative exposure level (CEL). Serum TSH, thyroglobulin (Tg), free thyroxine (FT4), and urinary iodine excretion (UIE) were measured in the laboratory. The difference in TSH concentrations according to CEL and other characteristics were analysed using the Mann-Whitney U test. A multiple linear regression model was used to evaluate the potential determinants of TSH., Results: The mean age was 50 (SD 9.4) years. The median concentrations of TSH, FT4, and Tg/FT4 ratio were 1.46 mIU/L, 1.17 ng/dL, and 6.23 × 10 2 , respectively. We observed that higher TSH concentrations were found among those with a higher Tg/FT4 ratio, were classified as high CEL, and had lower UIE or FT4., Conclusions: Our findings show that Tg/FT4 ratio, CEL, FT4, UIE concentrations, and post-spraying days were determinants of TSH concentrations among farmers with primary exposure to CPF. These results indicate that farmers are exposed to agents with thyroid-disrupting properties, thus supporting previous evidence showing the potential for thyroid disorders in agricultural populations exposed to pesticides., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: The percentage of infertility cases in this world is about 50%. Seahorses ( Hippocampus spp.) are widely used in traditional medicine. Several studies suggest that seahorses have ethnopharmacological characteristics, such as fertility, antioxidants, and antifatigue. The purpose of this study was to determine whether seahorse extract (SE) ( Hippocampus comes L.) has an effect on fertility and serum biochemistry in rats induced by depo medroxyprogesterone acetate (DMPA)., Materials and Methods: All animals were induced with 1.25 mg/kg BW of DMPA. Animals were grouped into five groups: namely aquadest, 1% CMC, and SE doses of 150, 225, and 300 mg/kg BW. The rats were gavage every morning from week 7 until 18. At the end of our study, semen from the vas deferens and blood from the heart were analyzed. We analyzed with a one-way analysis of variance and Bonferroni's post hoc tests (α 95%)., Results: The concentration of spermatozoa had a significant difference in dose of 150 mg/kg BW compared to other groups ( p = 0.04). In contrast, the motility ( p = 0.012) and viability of spermatozoa ( p = 0.007) were highly significant differences ( p < 0.05 and p < 0.01) at 300 mg/kg BW. Testosterone levels were not significantly ( p = 0.162; p > 0.05), but tended to increase at 300 mg/kg BW (11.01%). Nevertheless, serum biochemistry was insignificant ( p > 0.05) in all groups., Conclusion: SE ( Hippocampus comes L.) ameliorates fertility and serum biochemistry in rats induced by DMPA., Competing Interests: No disclosure., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Background: Mahkota Dewa [Phaleria macrocarpa (Scheff) Boerl.] fruit in vitro and in- vivo can decrease and prevent elevation of the blood pressure, lower plasma glucose levels, possess an antioxidant effect, and recover liver and kidney damage in rats. This study aimed to determine the structure and inhibitory activity of angiotensin-converting enzyme inhibitors (ACE) from the Mahkota Dewa fruit., Methods: The fruit powder was macerated using methanol and then partitioned by hexane, ethyl acetate, n-butanol, and water. The fractions were chromatographed on the column chromatography and incorporated with TLC and recrystallization to give pure compounds. The structures of isolated compounds were determined by UV-Visible, FT-IR, MS, proton ( 1 H-NMR), carbon ( 13 C-NMR), and 2D-NMR techniques encompassing HMQC and HMBC spectra. The compounds were evaluated for their ACE inhibitory activity, and the strongest compound was determined by the kinetics enzyme inhibition., Results: Based on the spectral data, the isolated compounds were determined as 6,4-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (1), 4,4'-dihydroxy-6-methoxybenzophenone-2-O-β-D-glucopyranoside (2) and mangiferin (3). IC 50 values of the isolated compounds 1, 2 and 3 were 0.055, 0.07, and 0.025 mM, respectively., Conclusion: The three compounds have ACE inhibitor and mangiferin demonstrated the best ACE inhibitory activity with competitive inhibition on ACE with the type of inhibition kinetics is competitive inhibition., (© 2023. The Author(s).)

Background: Despite being the oldest therapy for heart failure, the use of digoxin is still controversial due to the narrow margin of safety. In Indonesia, digoxin is still considered one of the treatments for heart failure. However, analysis of intoxication has never been reported. This study aims to analyze the occurrence of digoxin intoxication, rate of rehospitalization and one-year survival in heart failure patients under digoxin treatment., Methods: A cross section-observational study was conducted at Harapan Kita National Cardiovascular Centre from January 2017 to December 2018 on heart failure patients who received digoxin therapy and had data on serum digoxin level. Intoxication was defined as the presence of specific ECG alteration(s), at least one extra-cardiac symptom(s) and further classified as definite (serum digoxin >2 ng/mL), probable (serum digoxin 0.91-1.99 ng/mL), or possible (serum digoxin 0.5-0.9 ng/mL). Risk factors of intoxication were analyzed by Chi-square test, and one-year survival was analyzed with Kaplan Meyer method., Results: 54 of 195 patients (27.69%) were classified as having intoxication, consisting of 32 (16.41%) definite, 19 (9.74%) probable, and 3 (1.54%) possible. Renal insufficiency was revealed as a significant influencing factor of digoxin intoxication with RR 2.48 (CI 1.13-5.464, p=0.016). Overall one-year survival of patients receiving digoxin was 259 days in the intoxication group and 307 days in the non-intoxication group. One-year rehospitalization was 11.8% in patients who received digoxin and 29.2% in those without digoxin (p=0.085)., Conclusion: The proportion of digoxin intoxication in heart failure patients was 27.69%. Renal insufficiency was revealed as a significant influencing factor of intoxication. There was a tendency of reduced hospitalization in those who received digoxin., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Iron deficiency anemia (IDA) in heart failure (HF) is associated with poor functional capacity. Several studies reported the benefit of iron therapy in HF with IDA on improving functional capacity. Therefore, we attempt to investigate the effect of oral iron supplementation on functional capacity in HF patients with IDA., Results: A double blind randomized controlled trial was conducted in National Cardiovascular Center Harapan Kita Hospital Universitas Indonesia. A total of 54 HFREF patients with IDA were enrolled and randomized to either oral Ferrous Sulphate (FS) 200 mg three times a day or placebo with 1:1 ratio for 12 weeks. Primary outcome was functional capacity measured by a six-minute walk test. There were 41 participants completed the study (FS n = 22, placebo n = 19). Ferrous sulphate significantly improved functional capacity changes (46.23 ± 35 m vs -13.7 ± 46 m, p < 0.001, CI -86.8 to -33.2) compared with placebo groups respectively after 12 weeks intervention., Conclusions: Oral FS supplementation for 12 weeks significantly improved functional capacity in HF patients with IDA., Trial Registration: clinicaltrials.gov, NCT02998697. Registered 14 December 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02998697., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Objective: Indonesia is an archipelagic country with a mega biodiversity, among others, in the marine area. Seahorses ( Hippocampus spp.) are a marine fish known to have biocompounds used in traditional medicine "Jamu," such as Hippocampus comes L. (HCL). The present study aims to analyze and compare the chemical contents of cultured seahorse (CS) and natural seahorse (NS) extracts., Materials and Methods: The CS and NS were identified morphometrically. After freeze-drying, the seahorses were ground into powder with a grinder. The seahorse powder was extracted with ethanol and a water solvent. The extract contained biocompounds, proximate, amino acids, and steroids with high-performance liquid chromatography., Results: The study found unique characteristics of HCL. The highest yield was obtained in NS using a water solvent (18.6%). The biocompounds in seahorses consist of alkaloids and triterpenoids. The highest proximate of water content (11.03%) and ash content (42.50%) was found in NS. In addition, other compounds were also detected in CS, such as fat (7.48%) and protein (47.67%). Both of HCL's different sources had all essential and nonessential amino acids in which the highest concentration were in NS, i.e., L-arginine (56,537.22 mg/kg), L-lysine (17,794.17), glycine (113,649.80 mg/kg), L-proline (47,056.15), and L-alanine (43,451.81). The analysis of the steroid compound of the extract suggested the presence of steroid glycosides., Conclusion: The highest yield of the seahorse extract with a water solvent is about 18.6% and protein content of 47.67% in CS. The crude extract has alkaloids, triterpenoids, and glycine (113,649.80 mg/kg) in NS with water, suggesting the presence of steroid glycosides., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. -0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism ( p = 0.037) and decreased amino sugar and nucleotide sugar metabolism ( p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota.

Objectives: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used., Methods: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants., Results: The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/*6. TCPy concentrations were higher among participants with CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy., Conclusions: The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

Background: Focal onset epilepsy carries a higher risk of intractability than generalized onset epilepsy. Knowledge of the risk factors of intractability will help guide the treatment of children with focal epilepsy. In addition to risk factors present at initial diagnosis, the evolution of clinical and electroencephalographic features may also play a role in predicting intractability., Methods: A prospective cohort study was done on children aged one month to three years with newly diagnosed focal epilepsy. Initial treatment of carbamazepine was given according to a standard protocol after assessment of clinical manifestations, neurologic and developmental status, EEG, and brain MRI. Depending on response to therapy, subjects may also receive valproic acid or phenobarbitone following the protocol. Follow-up was done in the second week and every month thereafter. At the end of the study period, seizure type was re-assessed and a repeat neurological and developmental examination and EEG was obtained to evaluate the role of clinical and EEG evolution in predicting intractability., Results: Out of 71 subjects, 21 (29.6%) had intractable epilepsy at the end of the study period. Age of onset (p = 0.216) and neurological status (p = 0.052) were not associated with intractable epilepsy. On logistic regression analysis, evolution of seizure type (p < 0.001; RR 56.45; 95%CI 6.56 to 485.85) and evolution of background EEG rhythm (p < 0.001; RR 56.51; 95%CI 2.77 to 1152.16) were significantly associated with intractable epilepsy., Conclusions: Changes in seizure type and baseline EEG rhythm may predict intractability in children one month to three years of age with focal epilepsy., (Copyright © 2021. Published by Elsevier Inc.)

Background: Current standard management of diabetic foot ulcers (DFUs) consists of surgical debridement followed by soak NaCl 0.9% gauzes tight infection and glycaemic control. Nowadays the use of advanced platelet-rich fibrin (A-PRF) has emerged as an adjunctive method for treating DFUs. This study was conducted to demonstrate the ability of combine A-PRF + HA as a complementary therapy in DFUs healing related with angiogenesis,inflammation and granulation index process., Methods: This open label randomized controlled trial was conducted in Koja District Hospital and Gatot Soebroto Hospital Jakarta, Indonesia on July 2019-April 2020. DFUs patients with wound duration of three months, Wagner-2, with size of ulcer less than 40 cm 2 were included in the study. The number of subjects was calculated based on the rule of thumb and allocated randomly into three groups, namely topical A-PRF + HA, A-PRF and Sodium Chloride 0.9% as a control, for each of 10 subjects. A-PRF made by 10 mL venous blood, centrifuge 200 G in 10 min, meanwhile A-PRF + HA though mix both them with vertex machine around 5 min. Biomarker such as VEGF, PDGF and IL-6 examined from DFU taken by cotton swab and analysis using ELISA. Granulation Index was measured using ImageJ. Biomarkers and granulation index were evaluated on day 0, 3, 7 and 14. Data were analysed using SPSS version 20 with Anova and Kruskal Wallis test to compare the angiogenesis and inflammation effect between the three groups., Result: In topical dressing A-PRF + HA, there is an increase in delta VEGF on day-3 (43.1 pg/mg protein) and day-7 (275,8 pg/mg protein) compared to A-PRF on day-3 (1.8 pg/mg protein) and day-7 (104.7 pg/mg protein), also NaCl (control) on day-3 (-4.9 pg/mg protein) and day-7 (28.3 pg/mg protein). So that the delta VEGF of A-PRF + HA group increase significantly compared with others on day-3 (p = 0.003) and day- 7 (p < 0.001). Meanwhile A-PRF + AH group, there is also a decrease in delta IL-6 after therapy on day-3 (-10.9 pg/mg protein) and day-7 (-18.3 pg/mg protein) compared to A-PRF in delta IL-6 on day- 3 (-3.7 pg/mg protein) and on day-7 (-7.8 pg/mg protein). In NaCl (control) group there is a increase delta IL-6 on day-3 (4.3 pg/mg protein) and on day-7 (35.5 pg/mg protein). So that the delta IL-6 of A-PRF + HA group decrease significantly compared with others only on day- 7 (p = 0.015). In PDGF le level analysis, A-PRF + HA group increase significantly (p = 0.012) only in day -7 compare with other group (5.5 pg/mg protein)., Conclusion: The study shows the superior role of combined A-PRF + HA in the treatment DFU though increase angiogenesis and decrease inflammation pathway. The advantage of using A-PRF + HA is that it accelerates wound healing by increasing granulation tissue compared to A-PRF alone., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Carbamazepine (CBZ)-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are strongly associated with the HLA-B*15:02 allele. Screening HLA-B*15:02 before CBZ administration might prevent CBZ-induced SJS/TEN by enabling clinicians to prescribe alternative therapy for positive patients. Similar to other Southeastern Asian countries, HLA-B*15:02 is highly prevalent in Indonesia. Therefore, we assessed the economic value of HLA-B*15:02 screening before CBZ prescription to patients with epilepsy in Indonesia. A generic cost-effectiveness model and decision support tool, developed to enable users to perform an initial cost-effectiveness analysis from a healthcare provider/payer perspective, were used to assess the value of HLA-B*15:02 genotyping. The incremental cost-effectiveness ratio of adopting universal HLA-B*15:02 screening was 656,444,671 Indonesian Rupiah (IDR)/quality-adjusted life year (QALY) gained for patients compared with 2,634,975,574 IDR/QALY gained for providing valproic acid (alternative drug) without screening. Thus, neither HLA-B*15:02 screening nor substitution with VPA meets the Indonesian threshold for cost effectiveness. However, the improved outcomes with this test in other Asian countries may inform the desirability of implementation in Indonesia even with suboptimal cost-effectiveness., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Autologous platelet-rich fibrin (A-PRF) is an adjunctive method for diabetic foot ulcer (DFU) in addition to glycaemic control and debridement. This study aimed to evaluate the role of A-PRF + hyaluronic acid (HA), A-PRF and sodium chloride 0.9% (control) in DFU wound healing. Nowaday, the use of  PRF autologous consider as adjuvant therapy in DFU treatment., Methods: This open-label randomized controlled trial was conducted at Koja District Hospital and Gatot Soebroto Hospital from July 2019 to April 2020. DFU patients with wound duration of three months, Wagner-2, and ulcer size < 40 cm2 were recruited and randomly assigned into A-PRF + AH, A-PRF and control group. On day-0, day-3 and day -7, samples and photographs were taken. Samples were analysed with ELISA and photographs were analysed with ImageJ to calculate granulation index (GI). Statistical analysis was performed using SPSS version 20., Results: Topical therapy with A-PRF + AH was associated with a significant increase in VEGF from day 0 (232.8 pg/mg) vs day 7 (544.5 pg/mg) compared to A-PRF on day 0 (185.7 pg/mg) vs day 7 (272.8 pg/mg), and the controls on day 0 (183.7 pg/mg) vs day 7 (167.4 pg/mg). On evaluation  of VEGF swab, there is increasing significantly in A-PRF+HA group compare others group in day -3 ( p=0.022) and day -7 (p= 0.001).In the A-PRF + AH group, there was a significant decrease in IL-6 from day 0 (106.4 pg/mg) vs day 7 (88.7 pg/mg) compared with PRF on day 0 (91.9 pg/mg) vs day 7 (48,8 pg/mg). IL-6 was increased in the control group from day 0 (125.3 pg/mg) vs day 7 (167.9 pg/mg). On evaluation  of IL-6 swab, there is decreasing significantly in A-PRF+HA group compare others group in day -7 (p= 0.041)., Conclusion: The PRF + HA combination increased angiogenesis and reduced inflammation in DFUs and may represent a new DFU therapy.

Background: Agriculture is a major economic sector in Indonesia. Chemical pesticides are widely being used in agriculture for controlling pest. There is a growing concern that pesticide exposure, particularly chlorpyrifos (CPF) exposure, combined with other occupational characteristics that determine the level of exposure, can lead to further health impacts for farmers. Our objective was to evaluate the cumulative exposure characteristics among farmers exposed to CPF by using a validated algorithm., Methods: We conducted a cross-sectional study of 152 vegetable farmers aged 18-65 who actively used CPF for at least 1 year in Central Java, Indonesia. Subject characteristics were obtained using a structured interviewer-administered questionnaire, addressed for sociodemographic and work-related characteristics. The cumulative exposure level (CEL) was estimated as a function of the intensity level of pesticide exposure (IL), lifetime years of pesticide use and the number of days spraying per year. CEL was subsequently classified into two groups, high and low exposure groups. The difference in characteristics of the study population was measured using Chi-square, independent-t or Mann-Whitney test. Association between CEL and its characteristics variables were performed by multiple linear regression., Results: Seventy-one subjects (46.7%) were classified as the high exposure group. The use of multiple pesticide mixtures was common among our study population, with 94% of them using 2 or more pesticides. 73% reported direct contact with concentrated pesticides product, and over 80% reported being splashed or spilt during preparation or spraying activity. However, we found that the proportion of proper personal protective equipment (PPE) use in our subjects was low. Higher volume of mixture applied (p <  0.001) and broader acres of land (p = 0.001) were associated with higher cumulative exposure level, while using long-sleeved clothes and long pants (p <  0.05) during pesticide spraying were associated with lower cumulative exposure after adjusted for age and gender., Conclusions: These findings indicate an inadequate knowledge of using pesticides properly. Thus, we recommend comprehensive training on pesticide usage and encourage proper PPE to reduce the exposure level.

Background: The accumulation of unpaired α-globin chains in patients with β-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with β-thalassemia major., Purpose: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with β-thalassemia major., Methods: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions., Results: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio., Conclusion: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in β-thalassemia major.

Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced-stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF- κ B levels] effects, apoptotic index, and safety of Biocurcumin (BCM-95) as a radiosensitiser in cervical cancer. In this double-blind placebo randomised-controlled trial, we randomised 121 patients into 2 groups (BCM-95 or placebo). MDA and their NF- κ B levels and apoptotic index were measured before and after administering 24 Gy of radiation. MDA was identified using Wills' method, whereas NF- κ B was identified via ELISA. The apoptotic index was identified using TUNEL and DAPI staining. The clinical response was classified based on the RECIST. MDA levels before radiation were similar between both groups in per protocol and intention-to-treat (ITT) analyses ( p = 0.53 and p = 0.16, respectively). After radiation, MDA levels increased in both groups with no significant differences in per protocol and ITT analyses ( p = 0.52 and p = 0.18, respectively). NF- κ B levels before radiation were similar between the two groups in per protocol and ITT analyses ( p = 0.92 and p = 0.98, respectively). After radiation, the BCM-95 group showed an increase in the NF- κ B levels compared with the placebo group in per protocol analysis but not in ITT analysis ( p = 0.018 and p = 0.42, respectively). The BCM-95 group had a higher apoptotic index before radiation in per protocol analysis but not in ITT analysis ( p = 0.01 and p = 0.61, respectively). After radiation, the apoptotic index remained higher in the BCM-95 group in per protocol analysis but not in ITT analysis ( p = 0.04 and p = 0.91, respectively). There was no significant difference in complete response between the groups (per protocol, p = 0.61; ITT analysis, p = 0.90). Although BCM-95 can regulate ROS, NF- κ B, and apoptosis in human cervical cancer, it is not significant. Therefore, BCM-95 does not improve clinical response to radiation treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Sigit Purbadi et al.)

Background: the use of statin to lower blood cholesterol is often associated with bothersome adverse effects such as myopathy and liver dysfunction. NC120 is herbal lipid lowering drug containing red yeast rice (RYR) extract, guggulipid, and chromium picolinate, and expected to have better safety profile. The aim of this study was to evaluate the efficacy and safety profiles of NC120 in lowering blood lipid., Methods: this was a double blind randomized clinical trial comparing NC120 with placebo in subjects with hypercholesterolemia. Two capsules of NC120 or placebo were administered twice a day for 28 days. Blood total-cholesterol, LDL-cholesterol, and triglyceride were measured on day-0, day-7, and day-28. Unpaired t-test was used to compare study parameter between groups, and one-way ANOVA was used to compare within group., Results: 25 subjects received NC120 and 24 subjects received placebo. Significant decrease of total cholesterol and LDL-cholesterol were observed since day-7 in NC120 group, while the changes in placebo group were not significant at all time of observation. No significant decrease of triglyceride was observed in NC120 group and in placebo group. Side effects were minor and comparable between the two groups., Conclusion: NC120 is effective in reducing total cholesterol and LDL-cholesterol, but not triglyceride. This drug shows a good safety profile, and thus can be considered for patients who can not tolerate statin drugs.

Aim and Objective: The present study aims to investigate whether the antihyperglycemic effect of Murraya koenigii is mediated by antioxidant properties and insulin mimetic effect., Methods: Thirty Spraque - Dawley rats were induced hyperglycemia by streptozotocin and nicotinamide (STZ-NA). The STZ-NA diabetic rats were treated with an ethanolic extract of Murraya koenigii 200 mg/kg b.w and 400 mg/kg b.w. One group was treated with glibenclamide (1 mg/kg b.w). After the administration of Murraya koenigii extract and glibenclamide for four weeks, the rats were sacrificed. Blood and organ samples were collected under a fasting condition. The body weight and blood glucose levels were measured. Hepatic enzymes were determined using a commercial kit, protein levels were estimated by Bradford's method, and plasma insulin was assayed by an ELISA kit. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated by the TBA-Wills method and Ellman's method, respectively., Results: Ethanolic extract of Murraya koenigii showed a significant reduction in blood glucose level at both doses, 200 and 400 mg/kg b.w. In addition, Murraya koenigii exhibited a profound antioxidant effect with decreased MDA level and increased GSH level, particularly at the 200 mg/kg b.w. and significantly decreased the HOMA-IR index., Conclusions: The present study reveals that Murraya koenigii possesses antidiabetic activity and antioxidant effects on STZ-NA induced diabetes mellitus., Competing Interests: The authors declare no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Neuroglobin (Ngb) is highly expressed in the suprachiasmatic nucleus, and can regulate Per1 gene expression. It is still not known whether Ngb also influences Cryptochrome (Cry). Cry is implicated in hypertension and primary aldosteronism (PA) in mice. There is a strong correlation between Obstructive Sleep Apnea (OSA) and PA. We propose to prove that Ngb and Cry play a role in OSA with PA., Methods: Subjects were recruited consecutively from residents of Jakarta, Indonesia; subjects aged 30-65 years with moderate to severe OSA and hypertension were included in the study. OSA was diagnosed using an unattended type 2 portable monitor (Alice Pdx), hypertension was diagnosed when morning blood pressure exceeded 140/90 mmHg or when taking anti-hypertensive drugs. Serum concentration of aldosterone, renin, Cry1, Cry2 and Ngb protein were determined using ELISA method. Primary aldosteronism (PA) was defined as ARR ≥20., Results: Forty subjects were recruited, 26 male and 14 female, median age 52.5 years, BMI 27.46 kg/m2, and AHI 34.8 times/hour. We found 16 subjects with PA and 24 non PA. Cry1 and Cry2 did not correlate with ARR in PA and non PA groups. Ngb correlated positively with Cry1 (Spearman's rho = 0.455, p = 0.038) but not Cry2 in PA patients. Cry1 concentration decreased in severe hypoxia., Conclusions: Ngb correlates with Cry1 in OSA with PA. There is no correlation between Cry1 or Cry2 with PA., Competing Interests: The authors have declared that no competing interests exist.

Apium graveolens (celery) is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups ( n = 6). Group I was given captopril (10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally (40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography-mass spectrometry (LC-MS/MS) and from the blood data, the values of K e , C max , T max , T 1/2 , and area under the curve ( AUC ) were calculated. The results showed that oral administration of the celery extract increased C max (38.67%), T 1/2 (37.84%), and AUC (58.10%) and decreased K e (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril). In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy., Competing Interests: The authors declare no conflicts of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared. The HLA-B*15:02 allele was found in 66.7% of the patients with CBZ-induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio [OR]: 6.5; 95% CI: 1.2-33.57) and 22.9% of healthy controls (p = 0.0021; OR: 6.78; 95% CI: 1.96-23.38). These findings support the involvement of HLA-B*15:02 in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we also observed the presence of the HLA-B*15:21 allele. HLA-B*15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90-75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83-40]). Our findings suggest that screening for the HLA-B75 serotype can predict the risk of CBZ-induced SJS/TEN more accurately than screening for a specific allele.

Background: Cell culture techniques have many advantages for investigation of drug transport to target organ like liver. HepG2 and Huh-7 are two cell lines available from hepatoma that can be used as a model for hepatic drug transport. The present study is aimed to analyze the expression level of several drug transporter genes in two hepatoma cell lines, HepG2 and Huh-7 and their response to inhibitors., Materials and Methods: This is an in vitro study using HepG2 and Huh-7 cells. The expression level of the following drug transporter genes was quantified: P-glycoprotein/multidrug resistance protein 1, Organic Anionic Transporter Protein 1B1 (OATP1B1) and Organic Cationic Transporter-1 (OCT1). Ribonucleic acid was extracted from the cells using Tripure isolation reagent, then gene expression level of the transporters is quantified using Applied Biosystems quantitative reverse transcriptase polymerase chain reaction. Verapamil (P-glycoprotein inhibitor), nelfinavir (OATP1B1 inhibitor), quinidine (OCT1 inhibitor) were used to differentiate the inhibitory properties of these agents to the transporter expressions in HepG2 and Huh-7 cells., Results: Huh-7 shows a higher level of P-glycoprotein, OATP1B1 and OCT1 expressions compared with those of HepG2. Verapamil reduces the expressions of P-glycoprotein in HepG2 and Huh-7; nelfinavir reduces the expression of OATP1B1 in HepG2 and Huh-7; while quinidine reduces the OCT1 gene expressions in HepG2, but not in Huh-7 cells., Conclusion: This study indicates that HepG2 might be a more suitable in vitro model than Huh-7 to study drug transport in hepatocytes involving drug transporters.

Background: Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis., Objectives: To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes., Methods: Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery., Results: In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups., Conclusion: Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.

In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 μM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 μM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 μM concentration to 150% and 0.5 μM concentration to 200% of normoxic activity.

Aim: The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE)., Methods: Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue., Results: Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats., Conclusion: These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: This study was performed to assess the role of ischemic preconditioning on cardiomyocyte apoptosis after open heart surgery, based on morphology by transmission electron microscopy, caspase-3 activity, biochemical markers, and cardiac performance., Methods: 12 piglets were divided into 2 equal groups: an ischemic preconditioning group and a control group. Ventricular muscles were collected to examine apoptotic ultrastructure morphology and caspase-3 activity. Blood samples from the coronary sinus were obtained for measurement of tumor necrosis factor-α, malondialdehyde, and cardiac troponin I. Aortic blood samples were taken for lactate measurements before and after cardiopulmonary bypass. Cardiac performance was measured by echocardiography before and after surgery., Results: Cardiomyocyte apoptosis occurred postoperatively, as shown by ultrastructure observation. Caspase-3 activity was less in the ischemic preconditioning group than the control group (p < 0.05). Measurements of specific markers of cardiomyocyte injury also showed lower increases in the ischemic preconditioning group, although not significantly different. Clinical outcomes showed that ischemic preconditioning was able to preserve cardiac performance in terms of ejection fraction, cardiac index, and stroke volume index; these were statistically significant, except for lactate concentration., Conclusions: Cardiomyocyte apoptosis occurs after open heart surgery. Ischemic preconditioning can reduce cardiomyocyte apoptosis and improve cardiac performance. Laboratory findings showed that ischemic preconditioning prevents injury of cardiomyocytes and reduces lactate concentration, although not statistically significant.

The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 μM) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 μM) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.

A 12-month randomized double blind controlled trial was conducted among 182 Indonesian postmenopausal women aged 47 to 60 years to determine the effect of 100 mg/day soy isoflavone supplementation on vascular endothelial function such as vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO) and malondialdehyde (MDA) as oxidative stress marker. The subjects were randomized to the intervention group receiving tablets consisting of 100 mg soy isoflavones and calcium carbonate 500 mg, and to the control group receiving 500 mg calcium carbonate. The concentrations of VCAM-1, NO and MDA were measured at baseline, and postsupplementation at 6 months and 12 months. After supplementation, the MDA concentrations were significantly lower in the soy isoflavone group compared with the control group (p=0.001). The concentrations of VCAM-1 and NO were not affected (p=0.992 and p=0.759, respectively). In all group the MDA concentration increased compared with baseline concentrations but the relative change of MDA concentrations was significantly lower in the soy isoflavone group compared with the control group. This study demonstrates that supplemental intake of soy isoflavones for 6 months and 12 months had an effect on oxidative stress by decreasing MDA concentration, but did not improve vascular endothelial function.

Aim: to explore the effects of ritonavir and primaquine combination given as a single-dose or multiple-dose compared to ritonavir alone on ritonavir plasma concentration in the rats., Methods: in single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive primaquine 12.5 mg/kgBW or primaquine 12.5 mg/kgBW + ritonavir 10 mg/kgBW or primaquine 12.5 mg/kgBW + ketokonazole 10 mg/kgBW. Ketokonazole was used as positive control for inhibitor of primaquine metabolism. In the multiple-dose study, thirty Spraque Dawley male rats were randomly allocated to receive primaquine 12.5 mg/kgBW/day or primaquine 12.5 mg/kgBW/day + ritonavir 10 mg/kgBW/day or primaquine 12.5 mg/kgBW/day + rifampicin 100 mg/kgBW/day. Rifampicin was used as a positive control for inducer of primaquine metabolism., Results: in the single-dose study, ketokonazole increases the area under the plasma concentration (AUC) of primaquine (h45.8%, p<0.000), while the ritonavir decreases the AUC of primaquine (i64.6%, p<0.000). Multiple-dose study shows that both rifampicin and ritonavir decreases the AUC of primaquine by 60.2% (p<0.000) and 67.7% (p<0.000), respectively., Conclusion: concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect could result in the insufficient concentration of primaquine as anti-relapse therapy in malaria caused by Plasmodium vivax, which might lead to treatment failure with primaquine.

Aim: to explore the effects of chronic systemic hypoxia on myocardial structure and morphology. In addition, the goal of present study is to develop a hypoxia-induced heart failure model in rats., Methods: Sprague-Dawley male rats, weighing 220-250 g at the time of recruitment were randomly allocated into 7 groups (n = 4 per group), the control normoxia group was exposed to room air, while the hypoxia groups were caged in a plexiglas hypoxic chamber (8% O2 and 92% N2) for 28 days. Structural and morphological changes of ventricular myocardium were determined at day 28, while blood gas parameters were measured at day 1, 3, 7, 14, 21, and 28., Results: histopathologic and morphologic evaluation showed massive hypertrophy accompanied by damage of the intercalated disk (ID) structure, angiogenesis, necrosis, fibrosis, and apoptosis as a hallmark of ventricular remodeling. At the end of treatment, there were increases of LV (2.79 vs 3.71) and RV (1.72 vs 2.54) wall thicknesses, and also in hypertrophy index (from 3.19 to 5.74). Blood gas analysis revealed metabolic acidosis compensated by respiratory alkalosis. There was an observed decrease of blood gas parameters in hypoxia group compared to control group: PO2 (24.7 vs 96.4 mm Hg), PCO2 (18.2 vs 40.4 mm Hg), O2 saturation (25.5 vs 94.1 %), and HCO3 (10.1 vs 23.4 mmol/L). On the other hand an increase in hemoglobin level (221.5 vs 120.3 g/L), haematocrit level (68.6 vs 45.2 %), and red blood cell count (10.4 vs 6.9 μL/1000) could be observed., Conclusion: our data clearly show that chronic systemic hypoxia causes massive ventricular hypertrophy accompanied by severe structural and morphological impairment of ventricular myocardium, which eventually results in cardiac failure.

Aim: To investigate the expression of B-type natriuretic peptide-45 (BNP-45) gene which was induced by systemic chronic hypoxia, and whether these changes would be different from BNP-45 protein in the plasma and its mRNA in the ventricular myocardial. This study also aimed to test the hypothesis that systemic chronic hypoxia may cause heart failure., Methods: Although clinical use of BNP as a biomarker in heart failure is increasing, the specificity of BNP for heart failure is not robust, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Plasma BNP levels were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. Thus, elevated BNP levels do not necessarily reflect heart failure but may also result from cardiac ischemia. Sprague-Dawley male rats, weighing 220-250 g at the time of recruitment were randomly divided into 7 groups (n = 4 per group), the control normoxia group was exposed to room air, while the hypoxia group were caged in a plexiglass hypoxic chamber (8%O2 and 92% N2) for 1, 3, 7, 14, 21, and 28 days, respectively., Results: Our data clearly showed that plasma BNP-45 and ventricular BNP-45 mRNA concentration were markedly increased which reached its peak on day 21 after treatment., Conclusion: Regulation of BNP-45 gene expression occurred at transcription as well as post-transcription level. Systemic chronic hypoxia could result in heart failure, especially when the hypoxia is severe and prolonged.

Aim: to evaluate the effects of curcumin on total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in acute coronary syndrome patients., Methods: this study were conducted at Dr. Cipto Mangunkusumo General Hospital (RSUPN-CM), Persahabatan Hospital, MMC Hospital and Medistra Hospital, Jakarta. The study started from 1 May 2005 to 5 May 2006. Study Design was an interventional study which was a randomized double blind controlled trial to evaluate the effects of curcumin administration at escalating doses (low dose 3 times 15 mg/day, moderate dose 3 times 30 mg/day, and high dose 3 times 60 mg/day) on total cholesterol level, LDL cholesterol level, HDL cholesterol level, and triglyceride level in ACS patients., Results: a 75 ACS patients undergoing randomization participated in randomized controlled trial (RCT). Of the 75 ACS patients participating in that RCT, 67 received care at RSCM, 6 at Persahabatan Hospital, and 2 at MMC Hospital. As many as 63 patients were able to participate in the RCT up to its conclusion. There was no significant difference in age, sex, risk factor of dyslipidemia, DM, smoking, hypertension, CHD history in family, height, body weight and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure in the four groups of patients. This showed that the randomization performed was reasonably good. There was no significant difference in laboratory parameters, such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride, fasting blood glucose, blood glucose 2 hours PP, glyco Hb, triglyceride, Hb, Ht, leukocyte, thrombocyte, ureum, creatinine, SGOT, SGPT, in the four groups. There was no significant difference in types of ACS and locations of ACS in the four groups as well. There was no significant difference in statin medicatios (simvastatin), aspirin ACE inhibitor, and DM medications in the four groups. No patient used tiazolidindion. No significant difference was found in the percentage of compliance in the four groups of patients. The effects of curcumin on total cholesterol level and LDL cholesterol level, there was a trend that the lower the dose of curcumin, the higher the effect of reduction. For HDL cholesterol level, there was also a trend that the lower the dose of curcumin, the higher the effect of increase in HDL cholesterol level. However, for triglyceride the pattern was not the same, and the group of moderate-dose curcumin shoed the minimal effect of increase, followed by the low-dose curcumin and finally the high-dose curcumin that showed the highest effect of increase., Conclusion: the administration of low-dose curcumin showed a trend of reduction in total cholesterol level and LDL cholesterol level in ACS patients.

Objective: This study was designed to investigate the butyrylcholinesterase (BChE) and C5 variant phenotypes in a Javanese ethnic group in Indonesia. BLOOD-DONORS, MATERIALS AND METHODS: Random blood samples from a Javanese ethnic group were obtained from the Indonesian Red Cross Service. The donors were 40.09 +/- 9.53 years old, consisting of 358 (89.45%) males and 42 females (10.55%). The plasma content of BChE was determined spectrophotometrically using benzoylcholine as substrate, and phenotyping of BChE was performed using the inhibitors 10 microM dibucaine and 50 microM sodium fluoride. Phenotyping of the C5+ variant was carried out by means of polyacrylamide gel electrophoresis using a 7.5% (w/v) acrylamide slab gel and a 3% (w/v) acrylamide stacking gel, and stained with fast red azo dye., Results: The results show that of 398 samples studied, the average activities of BChE are 1.00 +/- 0.22 U/ml. 377 individuals (94.72%) show normal activities, whereas 21 individuals (5.78%) are below normal (< 0.690 U/ml). The mean +/- SD of dibucaine number (DN) is 83 +/- 5 and the fluoride number (FN) is 66 +/- 6. From this population we identified one individual with UA phenotype (total activity: 0.310 U/ml, DN: 62, and FN: 50). The frequency of C5+ variant in the population as detected by acrylamide electrophoresis is 21%., Conclusion: Our data indicate that the atypical allele of BChE is rare and that the C5+ variant is detected in high frequency in the ethnic Javanese of Indonesia.

Sarcolemmal vesicles were purified to a similar extent, 50- to 60-fold on a protein basis, from normal rat hearts and hearts subjected to 30 or 60 min of autolysis at 37 degrees C (total ischemia in vitro). Electron microscopic examination of the autolytic hearts revealed sarcolemmal discontinuities and other morphological characteristics typical of irreversible cell injury. Total contents and percentage composition of phospholipid classes did not differ between normal and autolytic hearts or between sarcolemmal preparations from these hearts. There was no increase in lysophospholipid contents of whole hearts or of purified sarcolemma after autolysis. Long chain acyl-CoAs or acylcarnitines did not accumulate in autolytic hearts under our experimental conditions. The molar long chain acyl-CoA: phospholipid ratio in isolated sarcolemma was extremely low (1:100,000). It increased 3-fold after autolysis but the increase was most probably the result of an increase in mitochondrial contamination of the sarcolemmal preparations from autolytic hearts. The molar long chain acylcarnitine: phospholipid ratio of isolated sarcolemma was much larger (1:100), but it did not change after autolysis. Experiments, in which radioactive amphiphiles were incorporated in isolated sarcolemma that was subsequently repeatedly washed, indicated that the lysophospholipid and acylcarnitine contents of isolated sarcolemma reflect the contents of sarcolemma in situ, but that sarcolemmal acyl-CoA is used for re-acylation reactions during purification, explaining the low acyl-CoA content of isolated sarcolemma. Na/K-ATPase and Na/Ca-exchange activities were markedly depressed in isolated sarcolemma from autolytic hearts. Our results suggest that sarcolemmal phospholipid breakdown and sarcolemmal amphiphile accumulation are not responsible for the structural and functional defects of the sarcolemma after autolysis.