Propolis is a resinous material gathered by honeybees from the buds and bark of certain trees and plants. In Japan, propolis is widely used as a health food and the Japanese believe that it can cure inflammation, heart disease, and even diabetes and cancer. Biological properties of propolis have become a point of particular interest recently.1) The most used formulation in folk medicine is the ethanol extract. 2)Chemical analysis indicated that propolis is a multicomponent mixture of various compounds with prevalence of flavonoids and phenolic acids.3) Several biological attributes such as anticancer, antioxidant, antimicrobial, anti-inflammatory and antibiotic activities have been reported for propolis.4) The standardization of propolis preparations is indeed difficult because of changes in chemical composition and pharmacological activities, resulting from variation in geographical and botanical origin.5) It is important to investigate their mechanisms of action in order to predict possible therapeutic and toxic effects, and to also use this information to develop and design new drugs that are even more effective for the prevention and treatment of cancer. We are interested in the effects of various natural products on cell growth in human cancer cells, as predictors of novel agents that may be useful in cancer chemoprevention or therapy.6) In this study, the inhibitory effects of propolis, a new preparation (CB Propolis) isolated from Brazilian propolis, on the growth of the human leukemia cell line U937 and on the synthesis of DNA, RNA and protein in U937 cells are discussed. MATERIALS AND METHODSChemicals Aqueous solution of propolis, 7) CB Propolis (the dried ethanol extract of Brazilian propolis), was obtained from a commercial supplier (ChatBlanc inc., Tokyo, Japan). Lyophilized CB Propolis is equivalent to 18.5 mg propolis per 100 ml. In this study propolis was diluted in dimethysulfoxide (DMSO) and filtered with a sterile filter prior to use, and then added at the appropriate final concentrations to cultures of U937 cells. Control cells were treated with the same amount of vehicle alone. The final DMSO concentrations never exceeded 0.5% (v/v). In this condition, we confirmed that apoptosis was not observed in U937 cells. Z-Asp-CH 2 -DCB (a wide-spectrum caspase inhibitor) was purchased from Peptide Institute (Osaka, Japan). The cells were treated with 100 mM inhibitor for 1 h before the treatment with propolis. [ Cell Lines and Cell Culture To examine the effects of propolis on cell proliferation, U937 human histiocytic lymphoma cells were obtained from the Japanese Research Resources Bank, Tokyo, Japan. The cells (4ϫ10 6 cells/ml) were grown in RPMI 1640 medium (Iwaki Co., Ltd, Tokyo) supplemented with 100 units/ml of penicillin, 100 mg/ml streptomycin and 10% heat-inactivated fetal bovine serum at 37°C under a humidified 95% air 5% CO 2 atmosphere, and passaged every 7 d. U937 cells had a doubling time of about 24-30 h under these conditions.Cell Proliferation Experiments Cells were inoculated at a d...

Background/Aims: Patients developing neonatal thyroid dysfunction following maternal hysterosalpingography (HSG) involving the use of oil-soluble iodinated contrast medium (ethiodized oil) have been reported. The present study aimed to investigate the frequency and risk factors for neonatal thyroid dysfunction following HSG. Methods: We studied 212 infants born to mothers who had become pregnant after undergoing HSG involving the use of ethiodized oil. Results: Five of the 212 infants tested positive during congenital hypothyroidism screening; this frequency (2.4%) was higher than the recall rate among first congenital hypothyroidism screening results (0.7%) in Tokyo, Japan. Two of the 5 screening-positive infants showed hypothyroidism, and 3 showed hyperthyrotropinemia. The urinary iodine concentrations in 4 out of the 5 screening-positive infants were 1,150, 940, 1,570, and 319 μg/l. The subjects were divided into thyroid dysfunction (n = 5) and normal thyroid function (n = 207) groups. The median dosage of ethiodized oil in the thyroid dysfunction group was significantly higher than in the normal thyroid function group (20 vs. 8 ml, p = 0.033). Conclusion: When infertile women undergo HSG, the dosage of oil-soluble iodinated contrast medium should be as low as possible to minimize the risk of fetal or neonatal thyroid dysfunction.

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Auxological data is the gold standard index of the therapeutic condition in CYP21A2 deficiency over a long-range period, whereas urinary pregnanetriol for 24 h (PT) is variable for a shorter-range period. Ideal PT levels in comparison with auxological data have not been reported. The main purpose of this study was to analyze ideal PT values as an index of optimal control for CYP21A2 deficiency. First, inter-daily fluctuation of PT was analyzed in one participant. PT levels were distributed over a wide range of 0.44–14.7 mg/day (n=42) in this participant, suggesting that the therapeutic condition should be judged by multiple PT samples. Second, the therapeutic periods of 15 participants with CYP21A2 deficiency were classified using auxological data and Cushing-like symptoms, and the PT levels were analyzed in each period retrospectively. The 95% confidence intervals for the means of the PT levels in the excessive, good and poor control periods were 0.03–1.25 (n=26), 1.23–2.09 (n=116), and 5.35–8.37 (n=72) mg/m2/day, respectively. In conclusion, 1.2–2.1 mg/m2/day of PT values can be used as an index of optimal control in CYP21A2 deficiency.

Background: Previous studies have reported a high prevalence of autoimmune thyroid disease (AITD) in adult patients with pulmonary arterial hypertension (PAH). The aim of this retrospective study was to determine the prevalence of AITD in children and adolescents with idiopathic PAH (IPAH). Methods and Results:The study group included 16 patients who had been diagnosed as having idiopathic PAH when they were younger than 15 years old; all were younger than 20 years of age. Thyroid function and antithyroid antibody levels were examined regularly at 6-12-month intervals and when there were clinical signs of thyroid dysfunction. In total, 7 patients (44%) had AITD; 2 patients developed Graves' disease, 2 developed silent thyroiditis, and 3 had antithyroid antibodies with euthyroidism. The duration after PAH onset and the prostacyclin (PGI2) treatment period were significantly longer in patients with AITD (7.6±2.1 and 7.4±2.3 years, respectively) than in patients without AITD (5.0±1.1 and 4.8±1.2 years, respectively; P<0.01 and P<0.05). Conclusions:The prevalence of AITD is high in children and adolescents with IPAH, so evaluation of thyroid function is important to prevent deterioration of right heart failure. (Circ J 2010; 74: 371 - 374)

Auxological data are the gold standard indexes of the therapeutic conditions in patients with CYP21 deficiency over long-term periods, whereas urinary pregnanetriol (PT) for 24 h has been used as an index for short-term periods. We previously reported that the range of 1.2–2.1 mg/m2/day of PT for 24 h (24-h PT) could be used as an index of optimal control in patients with CYP21 deficiency. The purpose of this study was to analyze the range of PT in the first morning urine samples (morning PT) as an index of optimal control in patients with CYP21 deficiency. First, the therapeutic periods of 15 participants (aged 2 yr and 5 mo to 17 yr and 4 mo) were classified into excessive, good or poor control periods using auxological data and Cushing-like symptoms, and 24-h PT levels were analyzed in each period, retrospectively. The 95% confidence intervals for the means of 24-h PT levels in the excessive, good and poor control periods were 0.24–2.24 (n=25), 2.88–4.92 (n=114) and 13.26–21.28 (n=72) mg/gCr, respectively. Subsequently, 24-h PT and morning PT levels collected on the same day were analyzed for 14 participants (aged 9 mo to 29 yr and 8 mo). There was a significant correlation between the above two PT levels (n=25, p<0.0001). When the 24-h PT range of the good control period, 2.88–4.92 mg/gCr, was adjusted by the correlation, the ideal morning PT range became 2.15–3.34 mg/gCr. In conclusion, a morning PT in the range of 2.2–3.3 mg/gCr can be used as an index of optimal control in patients with CYP21 deficiency.

Subjects who are heterozygous for thyroid stimulating hormone receptor (TSHR) gene mutations present various phenotypes that range from euthyroid to hyperthyrotropinemia. Similarly, heterozygous dual oxidase 2 (DUOX2) gene mutations result in variable phenotypes, such as transient congenital hypothyroidism, subclinical hyperthyrotropinemia, and euthyroid in children. Here, we describe an 8-year-old boy who had normal newborn screening results, but who developed nonautoimmune hypothyroidism at the age of 1 year and 8 months of age. He was heterozygous for previously reported R450H-TSHR mutation and heterozygous for a novel double mutant allele A1323T-DUOX2 and L1343F-DUOX2. He needed levothyroxine (l-T4) replacement therapy to keep serum TSH levels within normal limits; l-T4 dose of 2.01-2.65 μg/kg/day corresponded to the dose taken by children homozygous for R450H-TSHR and by children with permanent congenital hypothyroidism. Therefore, the coexistence of a heterozygous TSHR mutation and a heterozygous DUOX2 mutation may have affected the severity of his hypothyroid condition.

About 30% of children with elevated TSH levels during neonatal screening have a transient form of disorder. On the other hand, it has been reported that subclinical hypothyroidism persists in late childhood in about 30% of children found to be false-positive during neonatal screening. The aim of this study was to determine whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are influenced by genetic background. The TSH receptor (TSHR), thyroid peroxidase (TPO) and dual oxidase 2 (DUOX2) genes, for which it has been reported that heterozygous defects cause neonatal transient thyroid dysfunction, were analyzed. Nine children with transient thyroid dysfunction or subclinical hypothyroidism detected during neonatal screening were studied. One child was heterozygous for a TSHR gene mutation (R450H), and another child was heterozygous for a TPO gene mutation (P883S). No children with mutation of the DUOX2 gene were identified. Genetic background may contribute to development of transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening.