A study on prothrombogenic and antithrombogenic biomarkers in deep vein thrombosis following meta-epiphyseal cancellous bone traumatization in major orthopedic surgeries.

Background: This study was aimed to show differences in the mean values of Collagen I (Col I)/Nitric Oxide (NO), Collagen IV (Col IV)/NO, Tissue Factor (TF)/NO, and P-selectin (P-sel)/NO ratios between patients with DVT and those without DVT, following hip and knee meta-epiphyseal cancellous bone traumatization in major orthopedic surgeries. Methods: This is an observational prospective cohort study on 69 patients aged > 50 years, who had orthopedic surgery without thromboprophylaxis. Examination of serum Col I, Col IV, TF, P-sel, and NO biomarker levels were performed three times, i.e. before surgery, 72 hours and 144 hours after surgery. We looked for the differences in mean levels of biomarkers, and mean ratio values of the prothrombogenic/antithrombogenic (Col I/NO, Col IV/NO, TF/NO, P-sel/NO) at 72 hours and 144 hours post surgery between patients with DVT and those without. DVT events, which were confirmed at 144 hours post surgery by venography (with the exception of 8 cases where color Doppler ultrasound was done due to contrast usage contraindications). Results: DVTs were identified in 18 patients (26.1%). There were significant differences of mean levels in pre-surgical Col IV (p = 0.022) and 72 hours NO (p = 0.014) between patients with and without DVT. In addition, between the same two patient groups, significant differences were found in the mean values of the prothrombogenic/antithrombogenic ratios, i.e. Col IV/NO, TF/NO, and P-sel/NO at 72 hours post-surgery (p = 0.007, p = 0.028, and p = 0.049 respectively), with lower median values that were found in subjects with DVT. At 144-hours post surgery, the only significant ratio difference between the two groups was the mean values of Col IV/NO ratio (p = 0.014) with the median values that were higher than the median values at 72-hours post surgery . Conclusion: The incidence of DVT following traumatization of the meta-epiphyseal cancellous bone after major orthopedic surgeries in hip and knee is influenced by the balance of prothrombogenic and antithrombogenic factors as shown by the significant differences in Col IV/NO, TF/NO and P-sel/NO ratios at 72-hours and Col IV/NO ratio at 144 hours after surgery between DVT positive and DVT negative patients.

Study on the influence of adiponectin genetic variants and adiponectin levels among Indonesian women with polycystic ovary syndrome.

Background: Insulin resistance and central adiposity are frequent disorders in PCOS women, which are marked by biological marker dysregulation related to this metabolic abnormalities. Association between adiponectin and insulin resistance has been investigated in many studies, while only a few studies were done in PCOS patients. This study is to determine the association of T45G polymorphisms in Indonesian population with PCOS biological markers and their influence to adiponectin serum. Methods: Fifty-two PCOS patients and 52 normal ovulatory women without hyperandrogenism as control subjects were included. Blood samples were collected between day 3 and 5 of a spontaneous menstrual cycle at 7 to 9 am, after overnight fasting. Serum levels of FSH, LH, testosterone, SHBG, glucose, insulin, lipid profile and adiponectin were measured. Insulin resistance was estimated by HOMA-IR, HOMA-β, and SHBG. T45G gene polymorphisms were determined by PCR after genomic DNA was obtained from peripheral blood of patients and control subjects. Results: There were significant difference between PCOS and control group in term of BMI, LH, testosterone, SHBG, and FAI, but not significant to T45G gene polymorphisms frequency distribution. Adiponectin levels were lower in PCOS patients than control. There was an association between insulin resistance with PCOS. Among PCOS patients, no association between adiponectin LH, testosterone, SHBG, and FAI with T45G gene polymorphisms. T45G gene polymorphisms were more frequent in PCOS with low adiponectin levels compared to those with high adiponectin levels, although not significant statistically. Conclusion: T45G gene polymorphisms has no direct association with PCOS biological markers, but its association with adiponectin needs further study.

Proatherogenic or antiatherogenic high density lipoprotein type in acute coronary syndrome and healthy male person.

Aim: To make proatherogenic/antiatherogenic HDL type criteria using Apolipoprotein A-I (ApoA-I), Paraoxonase-1 (PON-1), Neopterin and HDL-cholesterol levels, which may be useful in clinical practice. Methods: This was a case control study recruiting 52 subjects with Acute Coronary Syndrome (ACS) and 30 control healthy subjects. HDL type was classifi ed into antiatherogenic and proatherogenic based on the levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol. Concentrations of ApoA-I was measured by immunoturbidimetry method, PON-1 was measured by colorimetric method, Neopterin was measured by ELISA, and HDL-C was determined by homogenous method. Univariate logistic regression analysis was done using ACS as a dependent variable and levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol as independent variables. Proatherogenic/antiatherogenic HDL type was determined by using ApoA-I, PON-1, Neopterin and HDL-cholesterol cut off and odd ratios. Results: Patient’s age was 50.89 + 12.63 year, HDL-C was 39.82 + 9.84 mg/dL, Apo A-1 was 119.77 + 32.05 mg/ dL, PON-1 was 41.26 + 18.19 kU/L, Neopterin was 16.22 + 38.10 nmol/L. Cut offs of ApoA-I, PON-1 and Neopterin successively were 124.5 mg/dL, 40.8 kU/L, and 7.016 nmol/L. On univariate logistic regression analysis showed that OR of ApoA-I, PON-1 and Neopterin respectively were 29.759 (95% CI : 4.074 – 217.382), 1.647 (95% CI : 0.412 – 6.586), 4.317 (95% CI : 1.098 – 16.977). Using scoring system, we concluded that total score > 18 was proatherogenic HDL type, and total score < 18 was antiatherogenic HDL type. With this scoring we found 78.85% had proatherogenic HDL type in ACS population. Conclusions: Dysfunctional HDL or proatherogenic/antiatherogenic HDL type can be predicted by using ApoA-I – PON-1 – Neopterin – HDL-cholesterol scoring system. Those with score of 18 are supposed to have antiatherogenic HDL type, and those with score of > 18 were having proatherogenic HDL type.

CYP2A6 gene polymorphisms impact to nicotine metabolism.

Nicotine is a major addictive compound in tobacco cigarette smoke. After being absorbed by the lung nicotine is rapidly metabolized and mainly inactivated to cotinine by hepatic cytochrome P450 2A6 (CYP2A6) enzyme. Genetic polymorphisms in CYP2A6 may play a role in smoking behavior and nicotine dependence. CYP2A6*1A is the wild type of the CYP2A6 gene which is associated with normal or extensive nicotine metabolism. In the CYP2A6 gene, several polymorphic alleles have been reported such as CYP2A6*4, CYP2A6*7, CYP2A6*9, and CYP2A6*10 which are related to decreasing nicotine metabolism activity. The variation of nicotine metabolism activity could alter nicotine plasma levels. Smokers need a certain level of nicotine in their brain and must smoke regularly because of nicotine’s short half-life; this increases the number of smoked cigarettes in extensive metabolizers. Meanwhile, in slow metabolizers, nicotine plasma level may increase and results in nicotine toxicity. This will eventually lower the risk of dependence.

The effect of polymorphism of the beta-2 adrenergic receptor on the response to beta-2 agonist in bronchial asthma patients.

AIM: To discover the role of beta2-adrenergic receptor (beta2-AR) polymorphism on the response to beta-2 agonist, particularly in coding amino acid at sequences 16 and 27 as well as adjacent nucleotides. METHODS: The study was conducted by nested case-control method with consecutive samples of asthma patients aged 15-60 years at the outpatient clinic, Department of Pulmonology in Dr. Wahidin Sudirohusodo General Hospital, Makassar. Twenty-eight patients were found irresponsive to terbutaline nebulation (increased FEV1 < 15%) and 56 patients were responsive (increased FEV1 > or =15%). DNA extraction and amplification were performed by PCR as well as polymorphism detection, which was done by automatic sequencing machine. RESULTS: The Arg 16 polymorphism did not have any effect on the response to terbutaline nebulation, but Gln 27 polymorphism did with OR 3.18. New polymorphism was found in nucleotide at 20th order before the start codon, it was T/C -20, which also has an effect on the response to terbutaline nebulation with OR 4.53. When the three polymorphisms were combined, the effect were greater with OR 11.11. It was found that age, gender, obesity, onset and ethnicity had no effect on the response to terbutaline nebulation. CONCLUSION: Polymorphism of the novel Gln 27 and T/C -20 (newly known) have an effect on the response to beta-2 agonist. Both combination and polymorphism of Arg 16 will bring greater effect on the response to beta-2 agonist.

The effects of zinc supplementation on the TNF-α profile and diarrhea in severely malnourished children of low income family.

Zinc deficiency has a great impact on growth and development, especially in malnourished children. Zinc is important in both local and systemic immunity. The aim of this study was to assess the impact of zinc supplementation on the cytokine, tumor necrosis factor α (TNF-α), and diarrhea in severely undernourished under-five children of low-income families. A randomized double blind pre-test post-test controlled design was selected. A group of 12-59 month-old children were given local food, and treated as control group (n=60), and another group (n=60) were given local food with 15 mg/5 ml zinc as intervention group. Zinc concentration was measured by atomic absorption spectrophotometer (AAS), and TNF-α concentration was determined by ELISA. Data on nutrient intakes were collected using 24-hour food recall method. The result of the study showed that after zinc intervention, zinc serum increased significantly, and TNF-α concentration decreased along with reduction of the duration and frequency of diarrhea. Zinc concentration increased 87.0% in the intervention group, while in the control group the increase was only 19.6%. There was a significant reduction of both serum and fecal TNF-α concentration after intervention (p<0.05). Severity and duration of diarrhea were reduced significantly in the intervention group compared to the control group (p<0.001). It was concluded that zinc intervention reduced the duration and severity of diarrhea through improvement of immunity, especially local immunity with TNF-α as biomarker.