Chitinase-3-like protein 1, matrix metalloproteinase-9, and monocyte chemoattractant protein-1 as potential biomarkers and treatment targets of adenomyosis.

OBJECTIVE: This study aimed to investigate the levels of chitinase-3-like protein-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 (MCP-1) in adenomyosis, as compared to normal myometrial tissue. These biomarkers may be useful for determining potential treatment targets. METHODS: This was a correlative, analytical, and observational study with a cross-sectional design. Participants with a diagnosis of moderate-to-severe adenomyosis, as determined through transvaginal ultrasonography and histological examination, and who underwent laparotomy or laparoscopic surgery for the treatment of adenomyosis, were enrolled in the study. Unlike other studies that recruited healthy women as controls, our study used adenomyotic and healthy nonadenomyotic myometria obtained from the same individual. The levels of CHI3L1, MMP-9, and MCP-1 in the biopsy samples were determined using enzyme-linked immunoassay kits, according to the manufacturer's protocol. RESULTS: A highly significant increase in the levels of CHI3L1, MMP-9, and MCP-1 was found in adenomyotic tissues compared to non-adenomyotic tissues (P<0.001). A significant positive correlation was found between CHI3L1 and MMP-9 levels (r=0.463; P=0.008), CHI3L1 and MCP-1 levels (r=0.594; P<0.001), and MCP-1 and MMP-9 levels (r=0.680; P<0.001) in adenomyotic tissues. CONCLUSION: CHI3L1 may play a role in the pathogenesis of adenomyosis via the regulation of the MCP-1 and MMP-9 pathways. Therefore, these molecules may serve as biomarkers and potential therapeutic targets for adenomyosis.

First Trimester Ferritin Is Superior over Soluble Transferrin Receptor and Hepcidin in Predicting Anemia in the Third Trimester: Result from a Cohort Study in Indonesia.

INTRODUCTION: Anemia in the third trimester has been identified as a risk factor for maternal and fetal morbidity that might lead to mortality. Due to its high cost, finding the best marker to predict anemia became more important to allow early prevention. Only one of ferritin, hepcidin, or soluble transferrin receptors can be picked for the prediction of anemia in the third trimester especially in low-resource setting. OBJECTIVE: This study aimed at defining the best marker among ferritin, hepcidin, or soluble transferrin receptor (sTfR) in the first trimester for prediction of anemia in the third trimester. Materials, Methods, and Setting. This diagnostic study was nested on the cohort study of vitamin D and its impact during pregnancy in Indonesia. Singleton pregnant mothers with normal fetus were recruited in the first trimester from four cities in West Java, Indonesia. The 304 pregnant women were screened for hepcidin, ferritin, and sTfR level in the sera. All biomarkers were measured by ELISA. Complete blood count (CBC) was done by impedance method measurement (SysmexR). Only subjects with complete data were included in analysis for diagnostic study to compare the three markers by finding the best receiver operating curve (RoC), likelihood ratio (LR), and risk estimate (RR). RESULT: One-hundred and eighty-one pregnant women were eligible for analysis. The result of this study showed that the serum ferritin level in the first trimester was the best marker to predict anemia in the third trimester of pregnancy. Hepcidin and sTfR performed poorly. A new cutoff point of ferritin level ≤27.23 ng/ml yielded the best ROC with 67% area under curve (95% CI 60%-75%, p < 0.0001, Youden index J 0.28), specificity 86.29% (95% CI 79.0%-91.8%), LR (+) 3.07 (95% CI 1.8-5.3), and RR 2.48 (95% CI 1.67-3.68). These last figures were better than the previously used cutoff point of ferritin level below 30 ng/ml. CONCLUSION: This study provided evidence that the serum ferritin level ≤27.23 ng/ml in the first trimester was the best marker to predict anemia in the third trimester. It was valuably useful for secondary screening of anemia in pregnancy, targeting subjects who may need rigorous approach for iron deficiency treatment in the prevention of anemia in pregnancy.

Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriosis Menstrual Blood.

Endometriosis is a gynecological disease characterized by the presence of endometrial-like tissue outside the uterine cavity. Remodeling of the extracellular matrix (ECM) is a prerequisite for tissue implantation. The presence of matrix metalloproteinase (MMP) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in shed endometrium cells has a significant role in ECM degradation. A case-control study was performed to find other diagnostic markers using menstrual blood. We examined a sample of 68 women who visited the gynecology clinic in Dr Hasan Sadikin General Hospital, 40% of whom were confirmed to have endometriosis, and the rest tested negative by histopathological examination. All endometriotic cases presented MMP-9 and TIMP-1 expression with different cell distribution. MMP-9 expression in endometriosis patients was increased compared to the controls (p = 0.002). Expression of MMP-9 in >80% of endometrial cells was associated with a higher risk for endometriosis (OR 4.44 95% CI 1.31 to 15.56) compared to MMP-9 expression in 50%-80% of cells. TIMP-1 cell expression in women with endometriosis was lower than in the control group (p = 0.030). Subjects with TIMP-1 expression in 20%-50% of endometrial cells had a higher risk for endometriosis (OR 4.5, 95%CI 1.21-17.42) compared those with TIMP-1 expression in 50%-80% of cells. These expressions levels can be useful to predict endometriosis.

Detection of endometriosis using immunocytochemistry of P450 Aromatase expressions in eutopic endometrial cells obtained from menstrual sloughing: a diagnostic study.

OBJECTIVE: To explore the possibility of a new diagnostic approach of endometriosis based on immunocytochemistry scoring of Aromatase P450 expressions in endometrial cells collected from menstrual sloughing. This is a case control study. Immuncytochemistry scores vs. histopathological examination in one tertiary- and secondary-level hospital in Bandung; two secondary level hospital in Garut and Sumedang, West Java, Indonesia. Thirty-five patients with and without endometriosis were enrolled. All subjects had diagnostic procedures for endometriosis suspicion, with addition menstrual blood samples for cytopathological examination. The specimens were sent for immunocytochemistry assessment of P450 Aromatase expressions (ICAPEC). The previous procedure resulted in cut-off point of histo score (H-score), sensitivity, specificity, (+) and (-) ICAPEC predictive value. RESULTS: The P450 Aromatase expression in endometrial cells of women with endometriosis was significantly stronger than without one. The cut-off point of H-scores to detect endometriosis was > 4. By this criteria, H-score had 94.6% sensitivity, 90.9% specificity, 92% positive predictive value and 93% negative predictive value. Immunocytochemistry scoring of Aromatase P450 expression in endometrial cells (ICAPEC) derived from menstrual blood specimen was a good candidate as alternatives approach in diagnostic procedure of endometriosis. Application and evaluation in clinical practice would provide the economically benefit in diagnostic procedure.

Association of first trimester maternal vitamin D, ferritin and hemoglobin level with third trimester fetal biometry: result from cohort study on vitamin D status and its impact during pregnancy and childhood in Indonesia.

INTRODUCTION: The role of vitamin D in placental functions and fetal growth had been addressed in many reports with conflicting results. However, such report is limited for Indonesian population. The aim of this study was to explore the association between maternal vitamin D level in the first trimester and fetal biometry in the later stage of pregnancy with adjusted OR for other determinants like hemoglobin and ferritin level. METHODS: From July 2016 a prospective cohort study of pregnant women had begun in four cities in West Java, Indonesia. Data on maternal vitamin D, ferritin, hemoglobin level, maternal demography and fetal biometry were analyzed with linear regression. RESULTS: Among 203 recruited women, 195 (96.06%) had hypovitaminosis D. One hundred fifty two (75%) were in deficient state and 43 women (21%) were in insufficient state. Women with insufficient vitamin D had the highest proportion of anemia, while women with normal vitamin D level had the highest proportion of low ferritin level. Maternal serum vitamin D showed significant associations with biparietal diameter (ß = 0.141, p = 0.042) and abdominal circumference (ß = 0.819, p = 0.001) after adjustment with maternal age, pre-pregnancy body mass index, parity, serum ferritin level, and hemoglobin level. CONCLUSION: Our study suggested that sufficient maternal vitamin D level was an important factor to improve fetal growth and development.

Correlation of Clinical Features, Laboratory Finding, and Pelvic Ultrasonography of Pulmonary Tuberculosis Women with Infertility.

BACKGROUND AND PURPOSE: The prevalence of tuberculosis (TB) in Indonesia is still high, whereas the prevalence of extra pulmonary tuberculosis such as female genital tuberculosis (FGTB) affecting infertility is unknown. FGTB caused irreversible severe damaged of tubes and endometrium, resulting in tubal occlusion and partial or total obliteration of the uterine cavity. Diagnosis of FGTB is difficult. Therefore, a prompt diagnosis and treatment of pulmonary TB in women can prevent fertility complications. This study aims to analyze the correlation of clinical features taken from the history, physical examination, investigation of blood laboratory and gynecological ultrasound of pulmonary tuberculosis women with infertility. PATIENTS AND METHODS: This was an observational analytic study with cross-sectional method. Subjects were women with pulmonary TB treated in TB-DOTS (tuberculosis-directly observed treatment, short-course) services at Dr Hasan Sadikin Hospital Bandung during December 2016 until March 2017. Subjects were divided into two groups consist of 32 TB patients with infertility, and 35 TB patients without infertility. RESULTS: The results showed that clinical features such as intermenstrual bleeding, endometrial synechiae, hydrosalpinx and endometritis appearance were the difference between two groups (p <0.001), those clinical features had a moderate correlation with the incidence of pulmonary tuberculosis women. CONCLUSION: Clinical features like endometrial synechia and ultrasound imaging such as hydrosalpinx and endometritis encountered in pulmonary and extra pulmonary tuberculosis patients with infertility can be used as a basis for the diagnosis of alleged genital TB.

Effect of Lead Nanoparticles Inhalation on Bone Calcium Sensing Receptor, Hydroxyapatite Crystal and Receptor Activator of Nuclear Factor-Kappa B in Rats.

This study aimed to investigate whether Pb nanoparticle exposure affects the bone calcium sensing receptor (CaSR), hydroxyapatite crystal, and receptor activator of nuclear factor-kappa B (RANK) in rats exposed to subchronic and chronic inhalation. Thirty two rats were randomly divided into eight groups. One group is a non-exposed group. While three groups were exposed to nanoparticles Pb at the following doses 6.25; 12.5; or 25 mg/m3 an hour daily for 28 days. Another three groups were exposed to nanoparticles Pb at following doses 6.25; 12.5; and 25 mg/m3 one hour daily for 6 months. The expression of trabecular CaSR was significantly decreased at the all doses subchronic exposure compared to the control group (P < 0.05). The CaSR expression significantly decreased in second and third doses subchronic exposure groups compared to the control groups (P < 0.05). With subchronic exposure, the crystal size was increased in second dose group and decreased in lowest and highest doses compared to the control (untreated) group. The crystal size and c-axis were decreased in all dose chronic exposures compared to the control (untreated) group. The expression of cortical RANK was significantly lower at the two lowest dose chronic exposures compared to the control group (P < 0.05). In conclusion, Pb nanoparticle inhibit hydroxyapatite crystal growth at least a part via down regulation of CaSR and RANK.