Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line

Estrogens, whether natural or synthetic, clearly influence reproductive development, senescence, and carcinogenesis. Pyrethroid insecticides are now the most widely used agents for indoor pest control, providing potential for human exposure. Using the MCF-7 human breast carcinoma cell line, we studied the estrogenic potential of several synthetic pyrethroid compounds in vitro using pS2 mRNA levels as the end point. We tested sumithrin, fenvalerate, d-trans allethrin, and permethrin. Nanomolar concentrations of either sumithrin or fenvalerate were sufficient to increase pS2 expression slightly above basal levels. At micromolar concentrations, these two pyrethroid compounds induced pS2 expression to levels comparable to those elicited by 10 nM 17ss-estradiol (fivefold). The estrogenic activity of sumithrin was abolished with co-treatment with an antiestrogen (ICI 164,384), whereas estrogenic activity of fenvalerate was not significantly diminished with antiestrogen co-treatment. In addition, both sumithrin and fenvalerate were able to induce cell proliferation of MCF-7 cells in a dose-response fashion. Neither permethrin nor d-trans allethrin affected pS2 expression. Permethrin had a noticeable effect on cell proliferation at 100 microM, whereas d-trans allethrin slightly induced MCF-7 cell proliferation at 10 microM, but was toxic at higher concentrations. Overall, our studies imply that each pyrethroid compound is unique in its ability to influence several cellular pathways. These findings suggest that pyrethroids should be considered to be hormone disruptors, and their potential to affect endocrine function in humans and wildlife should be investigated.     

Hyaluronic acid: a specific prognostic indicator of hepatic damage in biliary atresia

BACKGROUND/PURPOSE: Hepatic fibrosis can progress in biliary atresia (BA) and is associated with capillarization of hepatic sinusoids. The significance of serum hyaluronic acid (HA) as a noninvasive indicator of histological sinusoidal endothelial cell (SEC) damage and hepatic fibrosis in BA, is investigated. METHODS: A total of 28 postoperative BA patients (mean age, 11.0+/-3.7 years) and 20 normal controls (mean age, 10.5+/-2.8 years) were studied. BA patients were divided into group I, good liver function (n = 8); group II, moderate liver dysfunction (n = 10); and group III, severe liver dysfunction (n = 10). Serum HA was determined using a one-step sandwich enzyme immunoassay, and liver histological damage was confirmed immunohistochemically using an antibody against factor VIII-related antigen (FVIIIRAg), which is specific for detecting damaged SEC. RESULTS: Serum HA was significantly higher (P < .0001) in group III (84.6+/-36.5 ng/mL) than in group I (15.9+/-6.9 ng/mL) or group 11 (28.7+/-10.7 ng/mL). Although immunoreactive products of FVIIIRAg were abundant in group III, they were not detected in SEC from group II. CONCLUSION: Serum HA may be of value for monitoring postoperative BA patients as a noninvasive indicator of SEC damage and progressive hepatic fibrosis.     

Serum IFN-inducible protein-10: a new clinical prognostic predictor of hepatocyte death in biliary atresia

PURPOSE: The aim of this study was to determine whether chemokines such as serum IP-10 levels in patients with biliary atresia (BA) correlate with liver function and histology and assess its value as a medium to long-term prediction of prognosis in postoperative BA patients. METHODS: Thirty postoperative BA patients (mean age, 10.8+/-3.5 years) and eight normal controls (mean age, 10.3+/-3.3 years) were studied. The BA patients were divided into three groups according to liver function. Group I (n = 8) was jaundice free, had normal liver function and no evidence of severe cholangitis or portal hypertension. Group II (n = 12) had moderate liver dysfunction. Group III (n = 10), had severe liver dysfunction. Hepatic histology was assessed using conventional needle biopsy. Serum IP-10 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IP-10 in group III (458.0+/-240.0 pg/mL) were significantly higher than those in group II (233.6+/-126.9 pg/mL; P < .0001). Levels in group II were also significantly higher than those in group I (144.8+/-23.4 pg/mL; P < .05), but there was no significant difference between group I and controls (107.9+/-34.0 pg/mL). Liver biopsy findings showed a progression of fibrosis and mononuclear cell infiltration from group I to group III. There was intimal hyperplasia and swelling of endothelial cells of branches of the hepatic artery in the portal area in group III. CONCLUSION: Because IP-10 levels correlate closely with histological findings in postoperative BA patients, it would appear to play a specific role in hepatocyte death and hepatic artery changes, thus providing important information about progressive fibrosis in BA patients that facilitates treatment decision making and prediction of prognosis.     

Nitric oxide inhalation as a chemical assist for circulation in patients after cardiovascular surgery

The objective of this study was to investigate whether nitric oxide (NO) inhalation might be an alternative strategy as a chemical assist for the circulation in patients showing a deterioration in oxygen delivery. Twelve adult patients whose oxygen delivery indices (DO2I) were less than 400 ml/min/m2 after cardiovascular surgery were included in this study. NO was administered via a premixing system or a side stream system at doses between 1 and 10 (5.1+/-2.4) ppm. Data obtained before and during a 120 min NO inhalation were compared using the paired Student's t-test. The increase in PaO2/FiO2 resulting from NO inhalation was significant (from 162 to 251 mm Hg). DO2I increased significantly from 326 to 417 ml/min/m2 concomitantly with significant increases in both arterial oxygen content (CaO2) and cardiac index (CI) (from 14.1 to 15.4 vol% and from 2.31 to 2.71 L/min/m2 , respectively). The increase in SvO2 during NO inhalation was significant (from 55.2 to 62.6%). Among the other hemodynamic parameters, both total pulmonary resistance and systolic pulmonary arterial pressure (SPAP) showed significant decreases during NO inhalation, but right atrial pressure did not change significantly. There was a close relationship between the baseline SPAP level (bSPAP) and the decrease in SPAP during NO inhalation (dSPAP) (r = -0.88). However, negative correlations were observed between bSPAP and percentage increase in CI (%CI) (r = -0.61) and between bSPAP and percentage increase in DO2I (%DO2I) (r = -0.48). Moreover, positive relationships were observed between dSPAP and %CI (r = 0.62) and between dSPAP and %DO2I (r = 0.45). Hemoglobin (Hb) increased significantly from 11.0 to 11.4 g/dl. There were no significant changes in Fio2, pH, PacO2, or base excess (BE) during NO inhalation. The level of methemoglobin measured during the study period remained within the normal range (0.86+/-0.23%). In conclusion, NO inhalation could be an efficient and alternative assist for the circulation in patients whose oxygen delivery deteriorates after cardiovascular surgery.     

Use of mid-arm and head circumference to estimate gestational age and nutritional status of newborns]

1110 neonates, from 30 to 42 of estimated gestational age (EGA) were measured on the 1st day of life to estimate upper mid-arm circumference (MAC) and head circumference (HC). Individual MAC/HC ratio was calculated. MAC/HC ratio was used to estimate gestational age and nutritional status of the newborns. We proved that MAC/HC ratio increased linearly between 30 and 38 week of pregnancy and it stabilized between 38-42 week. We compared MAC/HC ratio with birth weight, skin fold score, and ponderal index. We concluded that this ratio may be very useful to estimate gestational age and to include the neonates to "the group of risk".     

Control of the RIA method as viewed from the standpoint of the investigation on the kinetics of the insulin-125I-antibody reaction

In this paper attempts were made towards the optimalization and the control of some parameters of the RIA reaction.Basing on the law mass action, as well as on the Scatchard's and Sips's equations, the equilibrium constants for the reversible reaction: insulin-¹²⁵I-antibody for different incubation temperatures were calculated. Moreover a characteristic of the antiinsulin antibody by means of the heterogeneity coefficient was done, as well as the values of the thermodynamic function increments were calculated, which made possible to point out explicitly the optimal shape of the standard curve.