Microproteinuria during Opisthorchis viverrini infection: A biomarker for advanced renal and hepatobiliary pathologies from chronic Opisthorchiasis

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of the participants had urine IgG against a crude OV antigen extract (OV antigen). We also observed that elevated levels of urine IgG to OV antigen were not associated with the intensity of OV infection, but were likely the result of immune-complex glomerulonephritis as seen in animal models of OV infection. Moreover, we observed that urine IgG to OV antigen was excreted at concentrations 21 times higher in individuals with APF and 158 times higher in individuals with CCA than controls. We also observed that elevated urine IgG to OV antigen could identify APF+ and CCA+ individuals from non-cases. Finally, individuals with urine IgG to OV antigen had a greater risk of APF as determined by Odds Ratios (OR = 6.69; 95%CI: 2.87, 15.58) and a greater risk of CCA (OR = 71.13; 95%CI: 15.13, 334.0) than individuals with no detectable level of urine IgG to OV antigen. Herein, we show for the first time the extensive burden of renal pathology in OV endemic areas and that a urine biomarker could serve to estimate risk for both renal and hepatobiliary pathologies during OV infection, i.e., serve as a “syndromic biomarker” of the advanced pathologies from opisthorchiasis

Long-term persistence of Opisthorchis viverrini antigen in urine: a prospective study in northeast Thailand

Antigen detected in urine for the diagnosis of opisthorchiasis has a low daily variation; however, the longer term variability in antigen concentrations is unknown. In this study, we prospectively monitored Opisthorchis viverrini antigen concentrations for 30 consecutive days and at subsequent monthly intervals in a cohort of opisthorchiasis-positive individuals. On the basis of the monoclonal antibody–based ELISA, the profiles of antigen-positive rate and antigen concentration exhibited no significant change over 30 days with a mean proportion positive of 87.1% (range 73.7%–100%), and the average antigen concentration was 29.7 ± 2.2 ng/mL (mean ± SE). The urine antigen concentration at baseline was similar to the subsequent measurements at 2, 4, 6, and 10 months in the follow-up study (P > 0.05). The consistency and low daily and long-term fluctuation of O. viverrini antigen in urine demonstrates the reliability of urine assay for diagnosis of opisthorchiasis

Glucose Tolerance Test and Pharmacokinetic Study of <i>Kaempferia parviflora</i> Extract in Healthy Subjects

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is a herbal medicine that has many potential pharmacological effects. The effect of KP extract on blood glucose level in rodent was reported. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3&#8242;,4&#8242;-pentamethoxyflavone (PMF) and 5,7,4&#8242;-trimethoxylflavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. Blood glucose levels of volunteers at 120 min after glucose loading were able to be returned to initial levels in placebo, KP 90 mg/day, and KP 180 mg/day groups both at baseline and 28-days of administration. The results of the pharmacokinetic study revealed that only TMF and PMF, but not 5,7-dimethoxyflavone (DMF) levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2&#8722;3 h. The maximum concentration (Cmax), area under the curve of blood concentration and time (AUC), and time to maximum concentration (Tmax) values of PMF and TMF estimated for the 180 mg/day dose were 71.2 &#177; 11.3, 63.0 &#177; 18.0 ng/mL; 291.9 &#177; 48.2, 412.2 &#177; 203.7 ng∙h/mL; and 4.02 &#177; 0.37, 6.03 &#177; 0.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on the glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development

General acts passed by the General Court of Massachusetts

Imprint varies.Vols. for 1915-19 published in 2 v.: General acts; Special acts.Vols. for some years issued in parts.Separate vols. issued for extra session, 1916, and for extra session, 1933.Vol. 12 (May 1831-Mar. 1833) in Jan. session, 1833; Jan. 1834-Apr. 1836 in vol. for extra session 1835/Jan. session 1836; May 1824-Mar. 1828; June 1828-June 1831, Jan. 1832-Apr. 1834, Jan. 1835-Apr. 1838, each bound with corresponding vol.Resolves issued separately, 1780-1838

Comparison of a urine antigen assay and multiple examinations with the formalin-ethyl acetate concentration technique for diagnosis of opisthorchiasis

Detection of worm antigen in urine is a sensitive diagnostic method for opisthorchiasis, particularly for light-intensity infections; however, the presence of eggs in feces is essential for validating results from the antigen assay. To address the issue of low sensitivity of fecal examination, we modified the protocol for the formalin-ethyl acetate concentration technique (FECT) and compared it against urine antigen measurements for detection of the parasite Opisthorchis viverrini. First, we optimized the FECT protocol by increasing the number of drops for examinations from the standard two drops to a maximum of eight. We were able to detect additional cases after examination of ≥ 3 drops, and the prevalence of O. viverrini saturated after examination of ≥ 5 drops. We then compared the optimized FECT protocol (examining five drops of suspension) against urine antigen detection for the diagnosis of opisthorchiasis in field-collected samples. The optimized FECT protocol detected O. viverrini eggs in 25 of 82 individuals (30.5%) who had positive urine antigen tests but were fecal egg negative by the standard FECT protocol. The optimized protocol also retrieved O. viverrini eggs in 2 of 80 antigen-negative cases (2.5%). In comparison with the composite reference standard (combined FECT and urine antigen detection), the diagnostic sensitivity of examining two and five drops of FECT and the urine assay was 58.2, 67, and 98.8%, respectively. Our results show that multiple examinations of fecal sediment increase the diagnostic sensitivity of FECT and thus provide further support for the reliability and utility of the antigen assay for diagnosis and screening of opisthorchiasis

Effects of day-to-day variation of Opisthorchis viverrini antigen in urine on the accuracy of diagnosing opisthorchiasis in Northeast Thailand

Antigen detection in urine using an enzyme-linked immunosorbent assay (ELISA) is more sensitive than fecal examination for diagnosis of opisthorchiasis and for assessment of the effects of drug treatment. It is not known whether day-to-day variation of urine composition, including levels of Opisthorchis viverrini antigen, influences the urine assay. We investigated this topic with the cooperation of participants from two localities in Northeast Thailand. Project participants were screened for parasite infections for three consecutive days using the quantitative formalin-ethyl acetate concentration technique (FECT) to detect O. viverrini eggs and the urine ELISA for detection of O. viverrini antigen. A subset of participants (n = 801) with matched fecal and urine samples were analyzed for comparison of inter-day prevalence estimates and the performance of the urine assay compared against FECT for diagnosis of opisthorchiasis. The daily prevalence measured by the urine assay ranged between 29.0%-30.2% while those by FECT ranged between 11.9%-20.2%. The cumulative three-day prevalence estimate determined by the urine antigen assay was 30.3%, which was significantly higher than that by FECT (20.2%, p < 0.05). A significant positive correlation was found between the concentration of antigen in urine and fecal egg counts (p < 0.001). Overall, the urine assay had better diagnostic performance for opisthorchiasis than fecal examination by FECT. The high sensitivity plus negligible daily variation of O. viverrini antigen in urine indicates the utility of the urine assay for diagnosis, as well as population screening, of opisthorchiasis

Diagnostic performance of urinary IgG antibody detection: A novel approach for population screening of strongyloidiasis.

The diagnosis of strongyloidiasis by coprological methods has a low sensitivity, underestimating the prevalence of Strongyloides stercoralis in endemic areas. Serodiagnostic tests for strongyloidiasis have shown robust diagnostic properties. However, these methods require a blood draw, an invasive and labor-intensive sample collection method, especially in the resource-limited settings where S. stercoralis is endemic. Our study examines a urine-based assay for strongyloidiasis and compares its diagnostic accuracy with coprological and serological methods. Receiver operating characteristic (ROC) curve analyses determined the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the urine ELISA, as well as estimates its positive predictive value and diagnostic risk. The likelihood ratios of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for each diagnostic positivity threshold. The urine ELISA assay correlated significantly with the serological ELISA assay for strongyloidiasis, with a D-Sn of 92.7% and a D-Sp of 40.7%, when compared to coprological methods. Moreover, the urine ELISA IgG test had a detection rate of 69%, which far exceeds the coprological method (28%). The likelihood of a positive diagnosis of strongyloidiasis by the urine ELISA IgG test increased significantly with increasing units of IgG detected in urine. The urine ELISA IgG assay for strongyloidiasis assay has a diagnostic accuracy comparable to serological assay, both of which are more sensitive than coprological methods. Since the collection of urine is easy and non-invasive, the urine ELISA IgG assay for strongyloidiasis could be used to screen populations at risk for strongyloidiasis in S. stercoralis endemic areas

Diagnostic performance of urinary IgG antibody detection: A novel approach for population screening of strongyloidiasis.

The diagnosis of strongyloidiasis by coprological methods has a low sensitivity, underestimating the prevalence of Strongyloides stercoralis in endemic areas. Serodiagnostic tests for strongyloidiasis have shown robust diagnostic properties. However, these methods require a blood draw, an invasive and labor-intensive sample collection method, especially in the resource-limited settings where S. stercoralis is endemic. Our study examines a urine-based assay for strongyloidiasis and compares its diagnostic accuracy with coprological and serological methods. Receiver operating characteristic (ROC) curve analyses determined the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the urine ELISA, as well as estimates its positive predictive value and diagnostic risk. The likelihood ratios of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for each diagnostic positivity threshold. The urine ELISA assay correlated significantly with the serological ELISA assay for strongyloidiasis, with a D-Sn of 92.7% and a D-Sp of 40.7%, when compared to coprological methods. Moreover, the urine ELISA IgG test had a detection rate of 69%, which far exceeds the coprological method (28%). The likelihood of a positive diagnosis of strongyloidiasis by the urine ELISA IgG test increased significantly with increasing units of IgG detected in urine. The urine ELISA IgG assay for strongyloidiasis assay has a diagnostic accuracy comparable to serological assay, both of which are more sensitive than coprological methods. Since the collection of urine is easy and non-invasive, the urine ELISA IgG assay for strongyloidiasis could be used to screen populations at risk for strongyloidiasis in S. stercoralis endemic areas

Effects of day-to-day variation of Opisthorchis viverrini antigen in urine on the accuracy of diagnosing opisthorchiasis in Northeast Thailand

Antigen detection in urine using an enzyme-linked immunosorbent assay (ELISA) is more sensitive than fecal examination for diagnosis of opisthorchiasis and for assessment of the effects of drug treatment. It is not known whether day-to-day variation of urine composition, including levels of Opisthorchis viverrini antigen, influences the urine assay. We investigated this topic with the cooperation of participants from two localities in Northeast Thailand. Project participants were screened for parasite infections for three consecutive days using the quantitative formalin-ethyl acetate concentration technique (FECT) to detect O. viverrini eggs and the urine ELISA for detection of O. viverrini antigen. A subset of participants (n = 801) with matched fecal and urine samples were analyzed for comparison of inter-day prevalence estimates and the performance of the urine assay compared against FECT for diagnosis of opisthorchiasis. The daily prevalence measured by the urine assay ranged between 29.0%-30.2% while those by FECT ranged between 11.9%-20.2%. The cumulative three-day prevalence estimate determined by the urine antigen assay was 30.3%, which was significantly higher than that by FECT (20.2%, p &lt; 0.05). A significant positive correlation was found between the concentration of antigen in urine and fecal egg counts (p &lt; 0.001). Overall, the urine assay had better diagnostic performance for opisthorchiasis than fecal examination by FECT. The high sensitivity plus negligible daily variation of O. viverrini antigen in urine indicates the utility of the urine assay for diagnosis, as well as population screening, of opisthorchiasis