Proceedings of the Korean Society of Toxicology Conference
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2006.11a
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pp.34-45
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2006
Chemical toxicants are metabolically converted to numerous metabolites in the body. Toxicokinetic characteristics of metabolites could be therefore used as biomarker of exposure for human risk assessment. Biologically based dose response (BBDR) model was proposed for future direction of risk assessment. However, this area has not been developed well enough for human application. Benzo(a)pyrene (BP), for example, is a well-known environmental carcinogen and may produce more than 100 metabolites and BPDE-DNA adduct, a covalently bound form of DNA with benzo(a)pyrene diolepoxides (BPDES), has been applied to qualitatively or quantitaively estimate human exposure to BP. In addition, di(2-ethylhexyl) phthalate (DEHP), a widely used plasticize. in the polymer industry, is one of endocrine-disrupting chemicals (EDCs) and has been monitored in humans using urinary or serum concentrations of DEHP or its monomer MEHP for exposure and risk assessment. However, it is difficult to estimate the actual level of toxicants using these biomarkers in humans using. This presentation will discuss a methodology of exposure and risk assessment by application of metabolic profiling kinetics.
Enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol was studied in fourteen women selected as the control subjects and ten infertile women in whom the infertility was appearing to be of endocrine origin. The extent of enterohepatic recycling of estriol ($E_3$) during the early follicular phase of menstrual cycle was assessed by monitoring during 48 h the urinary excretion of its two major metabolites i.e; estriol 16 $\alpha$-glucuronide ($E_3-16$$\alpha-G$) and estriol-3 glucuronide ($E_3$-3-G). The change in urinary level of $E_3$-3-G with respect to ($E_3-16$$\alpha-G$G was considered to reflect the extent of enterohepatic recycling of estriol. Lower values of urinary output of both metabolites in the infertile women as compared with the control subjects and the urinary excretion profile of both metabolites during 48 h after estriol ingestion reveal that the reduced extent of enterohepatic recycling could possibly be one of the factors which contribute towards the incidence of infertility in women.
The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. it provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.
Backgrounds/Aims: Central pancreatectomy (CP) is associated with a higher rate of postoperative pancreatic fistula (POPF), and it is less preferred over distal pancreatectomy (DP). We compared the short- and long-term outcomes between CP and DP for low-grade pancreatic neck and body tumors. Methods: This was a propensity score-matched case-control study of patients who underwent either CP or DP for low-grade pancreatic neck and body tumors from 2003 to 2020 in a tertiary care unit in southern India. Patients with a tumor >10 cm or a distal residual stump length of <4 cm were excluded. Demographics, clinical profile, intraoperative and postoperative parameters, and the long-term postoperative outcomes for exocrine and endocrine insufficiency, weight gain, and the 36-Item Short Form Survey (SF-36) quality of life questionnaire were compared. Results: Eighty-eight patients (CP: n=37 [cases], DP: n=51 [control]) were included in the unmatched group after excluding 21 patients (meeting exclusion criteria). After matching, both groups had 37 patients. The clinical and demographic profiles were comparable between the two groups. Blood loss and POPF rates were significantly higher in the CP group. However, Clavien-Dindo grades of complications were similar between the two groups (p = 0.27). At a median follow-up of 38 months (range = 187 months), exocrine sufficiency was similar between the two groups. Endocrine sufficiency, weight gain, SF-36 pain control score, and general health score were significantly better in the CP group. Conclusions: Despite equivalent clinically significant morbidities, long-term outcomes are better after CP compared to DP in low-grade pancreatic body tumors.
This experiment was carried out to estimate leaching potential of thirteen endocrine disruptor-suspected pesticides in upland soils using soil columns (5 cm I.D. ${\times}$ 35 cm H.) packed with soil A (sandy loam) and soil B (loam). When 12.6 mL of water, average precipitation in Cheongju area during the period from June to August, 2001-2010, was percolated through soil column packed with soil A every day for 21 days, no pesticides were detected from leachate, with the exception of metribuzin which was detected with negligible. Also, when 2 L of water was percolated consecutively five times through soil columns packed with soil A and B, irrespective of soil types, cypermethrin, endosulfan, fenvalerate, parathion and trifluralin, which were very low water solubilities and high soil $K_{oc}s$, were not detected from leachate and were distributed mostly in the depth of 0-5 cm, representing that water solubility and soil $K_{oc}$ are major contributing factors to their leaching behavior. Despite high average leaching rates in carbaryl and methomyl, actual possibilities of ground water contamination in the agricultural environment by them would be very low, considering that the negligible amount of pesticide was percolated through a lysimeter with an undisturbed soil core simulating the field conditions, while most of pesticide was percolated through a soil column with the disturbed soil profile.
Pancreases obtained from native Korean goats were used, and examined by immunoelectron microscopy using several antisera. Five types cells, glucagon (A), insulin (B), somatostatin (D), and pancreatic polypeptide (PP-I and PP-II) cells, were identified in the pancreatic islets. The morphologies of A, B, and D cells corresponded to the typical charateristics described in previous reports on other mammals. Serotonin immunoreactivity was observed in the D cells on the basis of the granular profiles. Two types of PP cells could be distinguished on the basis of the granular profile: the first type was formed by round, homogeneous secretory granules ($220{\sim}400nm$) having a narrow halo between the dense core and limiting membrane, while the other type consisted of cells whose secretory granules ($240{\sim}440\;nm$ in the major axis, $150{\sim}200nm$ in the minor axis) were pleomorphic, having a dense core and a closely fitting limiting membrane. From these results, we suggest that the pancreatic islets of the native Korean goat consist of five types of endocrine cells, A, B, D, PP-I and PP-II cells. Among these, PP-I type cells may correspond to the classical PP of other mammalian pancreases, while PP-II type cells may correspond to the enterochromaffin cells in other species.
In middle-aged men, abdominal obesity has been an important risk factor of coronary artery disease (CAD) as well as a predictor of hypertension, dyslipidemia, insulin resistance and glucose intolerance. Particularly, risks from abdominal obesity increase when adipose tissue accumulates in visceral compartment. Many studies showed that weight reduction by caloric restriction improves abdominal obesity and reduces lots of cardiovascular risk factors. Testosterone treatment also results in a significant decrease in visceral fat area and normalizes endocrine metabolism. However there is no study that compare the effect of caloric restriction with that of testosterone treatment. The purpose of this study is to investigate the effect of caloric restriction and that of testosterone treatment on body fat distribution, serum lipids and glucose metabolism in male patients with CAD. Forty five middle-aged overweight-obese men with CAD participated in 12 weeks' program. They were matched with age, body weight, body mass index (BMI) and divided into three groups : control group (n = 15) , caloric restriction group (-300 kcal/day, n = 15) and testosterone treatment group (testosterone undecanoate tablets, n = 15) . After 12 weeks, control group did not have any changes in anthropometries, lipid profile, body fat distribution, glucose metabolism and hormonal status. Expectedly, caloric restriction group showed decreases in body weight, BMI, waist to hip ratio, % body fat. Ten percentage of total cholesterol and 23% of triglyceride in serum were also decreased. In body fat distribution, total fat areas at both L1 and L4 levels were significantly reduced in this group without reduction in muscle of thigh and calf. However, testosterone treatment group did not have any significant changes in body weight, % body fat, serum lipid profile and abdominal fat distribution. In conclusion, weight reduction by caloric restriction is more beneficial in body fat distribution and serum lipid level than testosterone treatment in overweight male patients with CAD. This result suggests that modest weight reduction is possible to help decrease risk factors of CAD.
In general, the skeletal class III has the characteristics of mandibular overgrowth with a normal maxillary growth or maxillary undergrowth with a normal mandibular growth And clinical and radiographic evaluations of the patient are needed. However, the treatment plan is not dependent on these evaluations alone, because patient's general condition and hope for aesthetics varies. The aim of this report is to consider the treatment of a medically compromised patient with an anterior open bite and skeletal class III, which showed a severe mandibular overgrowth. In 2003, a 17-year-old boy with epilepsy, mental retardation presented at our clinic complaining of concave profile. A clinical examination showed severe mandibular prognathism with an anterior open bite. The radiographic examination revealed a short cranial base, a moderate maxillary overgrowth, severe mandibular overgrowth and skeletal open bite tendency. In 2004, he was verified to have no potential of growth by hand-and-wrist radiographs and an endocrine examination. He completed the preoperative orthodontic treatment and orthognathic surgery (sagittal split ramus osteotomy, genioplasty). He was evaluated on the first visit, the preoperative period and the postoperative period with a clinical and radiographic examination. At the first visit, the patient showed moderate overgrowth of the maxilla, severe overgrowth of the mandible, and a subsequential skeletal open bite. After the preoperative orthodontic treatment (preoperative period), the patient showed the same skeletal problem as before and a decompensated dentition for orthognathic surgery. After orthognathic surgery, his profile had improved, but he had still a skeletal openbite tendency because the maxillary orthognathic surgery was not performed. Severe mandibular prognathism with a maxillary overgrowth and anterior open bite should be treated by bimaxillary orthognathic surgery. However, one-jaw orthognathic surgery on the remaining the skeletal open bite tendency was performed for his medical problem and facial esthetics. This subsequential open bite should be resolved with a postoperative orthodontic treatment.
Proceedings of the Korea Society of Poultry Science Conference
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2003.11a
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pp.99-100
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2003
This experiment was conducted to investigate the effect of restricted feeding to pullet on growth and laying Performance, e99 qualify and endocrine profile in brown layers. 1,080 brown-layer chicks divided to three diet treatments, conventional diet and two restricted diets, for 70 weeks. Conventional diets(C) was formulated by NRC recommendation, and one of restricted diet started from seven to seventeen week of age(T1), and the other started from twelve to seventeen(T2). Overall egg Production was the highest in T1 (P<0.05) and there were not difference in C and T2. Average egg weight also showed similar to the tendency of egg production. Feed intake was higher in T1 during maximum production(P<0.05), but there were not difference in all treatments after the peak. Overall feed conversion ratio improved in T1 compared to C and T1(p<0.05). Egg shell thickness and egg shell strength tended to weak in aging, but there were not significant difference by treatments. Haugh unit also tended to similar to egg shell quality. Concentration of IGF-1 was influenced by feed intake. That of T1 maintained in low concentration compared to C during restriction period. The concentration of IGF-1 was decreased dramatically after the first egg. Estradiol concentration increased slightly at twelve week, and surged greatly near the first egg. Those of profile showed similar tendency of the first egg during laying period.
Differential gene expression profiling was performed in the hepatic tissue of marine medaka fish (Oryzias javanicus) after exposure to benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), by heterologous hybridization using a medaka cDNA microarray. Thirty-eight differentially expressed candidate genes, of which 23 were induced and 15 repressed (P<0.01), were identified and found to be associated with cell cycle, development, endocrine/reproduction, immune, metabolism, nucleic acid/protein binding, signal transduction, or non-categorized. The presumptive physiological changes induced by BaP exposure were identified after considering the biological function of each gene candidate. The results obtained in this study will allow future studies to assess the molecular mechanisms of BaP toxicity and the development of a systems biology approach to the stress biology of organic chemicals.
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