Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis.

OBJECTIVE: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT). DESIGN: Retrospective cohort study. SETTING: University hospital. POPULATION: A total of 33 deliveries after 22 weeks' gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016. METHODS: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver-operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth. MAIN OUTCOME MEASURES: Preterm birth before 34 weeks' gestation. RESULTS: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75). CONCLUSIONS: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT. TWEETABLE ABSTRACT: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.

Increased risk of mammary carcinoma development following transplacental and trans-breast milk exposure to a food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in Sprague-Dawley rats.

Effects of transplacental and trans-breast milk exposure to a food-derived mammary and colon carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), were investigated in rats. Female Sprague-Dawley rats were administered PhIP in the diet (100 ppm) for 4 weeks before mating with nontreated males and also during gestation and lactation. As controls, additional females were maintained on the basal diet without PhIP and mated as with the treated animals. The offspring of both groups were subdivided for each sex at weaning into three dietary groups receiving 100, 25, and 0 ppm and were killed at 47 weeks of age. Effects of the transplacental and neonatal exposure to PhIP on mammary carcinogenesis were most evident in females administered 25 ppm PhIP after weaning; the incidence and multiplicity of adenocarcinomas in offspring from the PhIP fed dams (42.9%, 0.62/rat) was significantly higher than the value for offspring from nontreated dams (4.8%, 0.05/rat). Furthermore, in the basal diet groups, the incidence of adenocarcinomas in females was higher, albeit not significantly, in offspring of the PhIP-treated than the nontreated dams (16.7%, 0.22/rat as compared with 3.3%, 0.07/rat). Although the highest incidence of mammary adenocarcinomas was found in the female progeny given 100 ppm PhIP from PhIP-treated dams (70.0%, 1.55/rat), this was only slightly higher than the 61.9% and 0.90/rat of the same dose group from the nontreated dams. In males, no apparent effects of transplacental and neonatal exposures were evident. In a separate experiment, excretion of PhIP into breast milk and transfer of PhIP to fetuses and neonates with resultant hepatic PhIP-DNA adduct formation were demonstrated. Thus, maternal exposure to this food-derived carcinogen may be a critical risk factor for generation of mammary carcinomas.

Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.

The present study is part of a program to obtain effective chemopreventive agents with low toxicity from medicinal herbs and traditional herbal medicines. We previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix) inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the present investigation, we found Sanshishi (Gardeniae fructus) and the traditional herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively. Adverse effects, evidenced by body weight loss, were weaker with OGT than component herbs. To investigate their mechanisms of action, the influence on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied. Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably contributing to their suppressive effects on ACF development. The results suggest that OGT may be useful for colon cancer chemoprevention in terms of efficacy and toxicity.

Suppression of azoxymethane-induced aberrant crypt foci in rat colon by nimesulide, a selective inhibitor of cyclooxygenase 2.

Non-steroidal anti-inflammatory drugs, such as piroxicam and sulindac, are known to inhibit development of aberrant crypt foci (ACF) and cancer in the colon. However, these agents cause gastrointestinal side-effects. Nimesulide is a selective inhibitor of cyclooxygenase 2 and has been shown to have a more potent anti-inflammatory action than piroxicam, but be less ulcerogenic and, therefore, a potentially more useful chemopreventive agent. To assess this possibility the inhibitory effects of nimesulide on the formation of ACF induced by azoxymethane in rat colon were investigated, and compared with those of piroxicam and sulindac. Male F344 rats were treated s.c. with 15 mg/kg body weight azoxymethane once a week for 2 weeks and given 50, 100 or 200 ppm nimesulide, 200 ppm piroxicam, or 200 ppm sulindac in their diet from the day before the first carcinogen treatment until the end of the experiment at week 4. At this time, nimesulide at doses of 50, 100 and 200 ppm had reduced the numbers of azoxymethane-induced ACF to 75%, 71% and 65% respectively compared to the control. The number of azoxymethane-induced ACF per colon in the group given 200 ppm nimesulide was almost the same as in those given 200 piroxicam, and lower than that in the group given 200 ppm sulindac. These results suggest that nimesulide, a selective cyclooxygenase 2 inhibitor, warrants attention as a candidate for chemopreventive agent with low toxicity, active against colon carcinogenesis.

Quantification of genistein and genistin in soybeans and soybean products.

It has been suggested that the isoflavone, genistein,, may have some role as a chemopreventive agent against cancer in humans. Levels of genistein and its beta-glucoside conjugate, genistin, ingested in soybeans and related bean products by the Japanese were quantified by HPLC, to estimate daily intake of these compounds. Amounts of genistein and genistin in soybeans, soy nuts and soy powder were in the range of 4.6 to 18.2 and 200.6 to 968.1 micrograms/g food, respectively. The values for soy milk and tofu (bean curd) were 1.9 to 13.9 and 94.8 to 137.7 micrograms/g food, respectively. Levels of isoflavones in fermented soybean products, miso (bean paste) and natto (fermented soybeans), were 38.5 to 229.1 micrograms/g food for genistein and 71.7 to 492.8 micrograms/g food for genistin. Thus, the level of genistein in the fermented soybean products was higher than in soy beans and soybean products such as soy milk and tofu. From these observations, it is suggested that the beta-glycosyl bond of genistin is cleaved to produce genistein by microbes during fermentation to yield miso and natto. Soy sauce was also found to contain both isoflavones, but at levels lower than in miso and natto. On the basis of these data for average annual consumption of soybeans and related products, daily intake of genistein and genistin by the Japanese is calculated to be 1.5-4.1 and 6.3-8.3 mg/person, respectively. These levels are much higher than those for Americans or Western Europeans, whose mortality rates for breast, colon and prostate cancers are greater than the Japanese.

Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide: a preliminary observation in the Japanese male population.

Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop suicidal behavior. Genetic factors for suicidal behavior have been observed in family, twin, and adoption studies. Because alcohol dehydrogenase (ADH1B) His47Arg and mitochondrial aldehyde dehydrogenase (ALDH2) Glu487Lys single nucleotide polymorphisms (SNPs), which affect alcohol metabolism, have been reported to exert significant impacts on alcohol consumption and on the risk for alcoholism in East Asia populations, we explored associations of the two functional SNPs with suicide using a case-control study of 283 completed suicides and 319 control subjects in the Japanese population. We found that the inactive ALDH2 allele (487Lys) was significantly less frequent in the completed suicides (19.3%) than in the controls (29.3%), especially in males, whereas this was not the case in females. The males bearing alcoholism-susceptible homozygotes at both loci (inactive ADH1B Arg/Arg and active ALDH2 Glu/Glu genotypes) have a 10 times greater risk for suicide compared with the males bearing alcoholism-protective homozygotes at both loci. Our data show the genetic impact of the two polymorphisms on suicidal behavior in the Japanese population, especially in males. Because we did not verify the daily alcohol consumption, the association of these SNPs with suicide might be due to alcoholism itself. Further studies using case-control subjects, which verifies the details of current and past alcohol consumption and diagnosis for alcoholism, are required to confirm these findings.

Inhibitory effect of Coptidis Rhizoma and Scutellariae Radix on azoxymethane-induced aberrant crypt foci formation in rat colon.

This study was conducted to obtain effective cancer chemopreventive agents with low toxicity from medicinal herbs. The effect of aqueous extracts from 9 medicinal herbs with antiinflammatory effect were examined on the formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions of the colon. Male F344 rats were treated with 15 mg/kg body weight of AOM once a week for two weeks. Herbal extract consisting of 2% of the diet was administered from 1 d prior to the first carcinogen treatment. The number of AOM-induced ACF per colon was counted at 4 week. Extracts of Coptidis Rhizoma and Scutellariae Radix significantly inhibited AOM-induced ACF formation. The number of ACF was decreased to 54% and 78% of that of the control by 2% Coptidis Rhizoma and Scutellariae Radix extract in the diet, respectively. Berberine and Baicalin, major ingredients of Coptidis Rhizoma and Scutellariae Radix, inhibited ACF formation at a dose equivalent to the amount in each herbal extract. Therefore, to investigate the mechanisms of action of berberine and baicalein which is the active substances of orally administered baicalin, their effects on cyclooxygenase 1 and 2 activities were studied. Berberine was found to inhibit cyclooxygenase 2 activity without inhibition of cyclooxygenase 1 activity, and baicalein inhibited cyclooxygenase 1 activity. Thus, Coptidis Rhizoma and Scutellariae Radix suppressed experimental colon carcinogenesis, and their chemopreventive effects were explained from the inhibition of berberine on cyclooxygenase 2 activity and baicalein on cyclooxygenase 1 activity.

Suppression of azoxymethane-induced rat colon carcinoma development by a fish oil component, docosahexaenoic acid (DHA).

The effects of intragastric gavage administration of docosahexaenoic acid (DNA) , a major component of fish oil, on azoxymethane (AOM)-induced colon carcinogenesis in rats was investigated. Male F344 rats were treated with 15 mg/kg body wt of AOM once a week, for two weeks. The animals were given either 1 ml of DHA or water intragastrically 5 times a week, starting the day before the first carcinogen treatment. The numbers of AOM-induced aberrant crypt foci in the rats given DHA were 76% and 62% of the control values, at 4 and 12 weeks, respectively. After 36 weeks of DHA treatment, colon tumors were counted and examined histologically. The blood plasma levels of prostaglandin E2 (PGE2) and polyunsaturated fatty acids were also quantified. The incidences of colon cancer did not differ, being 96% and 92% in the AOM and AOM+DHA groups, respectively. Colon cancer multiplicity was, however, significantly decreased by the DHA treatment; 3.65 +/- 2.18 in the AOM group and 2.41 +/- 1.58 in the AOM+DHA group (P <0.01). Notably, the numbers of moderately differentiated adenocarcinomas in the middle and distal colon in the DHA-treated group were lower than in the AOM group. The levels of PGE2 and arachidonic acid in the blood plasma of DHA-treated rats were also significantly lower than in the AOM group. These results suggest that DHA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting the arachidonic cascade.

Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) suppress colon carcinogenesis in man and experimental animals. However, conventional NSAIDs inhibit both cyclooxygenase (COX) isoforms, COX-1 and COX-2, and cause gastrointestinal side-effects. Nimesulide, a selective inhibitor of COX-2, is much less ulcerogenic. We, therefore, examined its influence on the development of intestinal polyps in Min mice. Female Min mice at 4 weeks old were given 400 ppm nimesulide in their diet for 11 weeks. This treatment resulted in a significant reduction of the numbers of both small and large intestinal polyps, the total being 52% of that in untreated control Min mice. The size of the polyps in the nimesulide-treated group was also significantly decreased. The results suggest that nimesulide is a good candidate as a chemopreventive agent for human colon cancer with low toxicity.

Simultaneous determination of byak-angelicin and oxypeucedanin hydrate in rat plasma by column-switching high-performance liquid chromatography with ultraviolet detection.

A simple and sensitive column-switching HPLC method was developed for the simultaneous determination of two furocoumarin compounds, byak-angelicin and oxypeucedanin hydrate, which are the main components of hot water extract of Angelica dahurica root (AE), in rat plasma. Plasma sample was simply deproteinated with perchloric acid. After centrifugation, the supernatant was injected into a column-switching HPLC system consisting of a clean-up column (Symmetry Shield RP 8, 20x3.9 mm I.D.) and analytical column (Symmetry C18, 75x4.6 mm I.D.) which were connected with a six-port switching valve. The flow-rate of the mobile phase (acetonitrile-water, 20:80) was maintained at 1 ml/min. Detection was carried out at wavelength 260 nm with a UV detector. The column temperature was maintained at 40 degrees C. The calibration curves of byak-angelicin and oxypeucedanin hydrate were linear over the ranges 19.6 to 980 ng/ml (r2>0.997). The accuracy of these analytes was less than 4.4%. The intra- and inter-day relative standard deviations of byak-angelicin and oxypeucedanin hydrate were within 12.0% and 12.7%, respectively. The present method was applied for the analysis of plasma concentration from rats after administration of AE.

Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice.

The effects of nimesulide, a selective inhibitor of cyclooxygenase-2 (COX-2) on azoxymethane (AOM)-induced colon carcinogenesis were investigated in mice. AOM at a dose of 10 mg/kg body wt was administered to male ICR mice once a week for 6 weeks. The animals were fed on AIN-76A powder diet containing nimesulide at doses of 200 or 400 p.p.m., starting the day before the first carcinogen treatment until the end of the experiment, at week 30. Administration of nimesulide reduced the incidence of colon carcinomas to 32 and 25% for the AOM + 200 and 400 p.p.m. nimesulide groups, respectively, compared with the AOM + basal diet group (50%). Multiplicities of colon carcinomas in the 200 and 400 p.p.m. nimesulide-treated groups were 0.70 +/- 0.28 and 0.35 +/- 0.11, respectively, being significantly smaller than the AOM alone value (1.79 +/- 0.47). The sizes of the colon carcinomas in the nimesulide-treated groups were also decreased. No significant influence on liver and lung tumor development was apparent. Thus, nimesulide exerted a suppressive effect on AOM-induced colon carcinogenesis in mice.