Changes of serum alpha 2u-globulin in the subacute oral toxicity study of ethynyl estradiol and bisphenol A based on the draft protocol for the 'Enhanced OECD Test Guideline No. 407'

To investigate the usefulness of serum alpha 2u-globulin changes as a new parameter for detecting endocrine-mediated effects, we performed a 28-day repeated-dose toxicity study using the administration of bisphenol A (BPA) or ethynyl estradiol (EE) in male rats, based on the draft protocol of the 'Enhanced OECD Test Guideline 407 (enhanced TG 407)'. BPA at doses of 0, 40, 200 and 1000 mg/kg per day or EE at doses of 0, 15, 75 and 375 microg/kg per day were orally administered to SD rats. The highest dose of BPA was reduced to 600 mg/kg per day from the second week of the study onwards because a male rat given 1000 mg/kg per day of BPA died within the first week, showing toxic clinical signs. In the assay using BPA, a reduction in the level of alpha 2u-globulin was detected in the group receiving a dose of 600 mg/kg per day. Reductions in the absolute and relative ventral prostate weights were only observed in the 600 mg/kg per day group. In the assay using EE, the alpha 2u-globulin level decreased significantly in the 375 microg/kg per day group. A reduction in the absolute and relative dorsolateral prostate weights was also observed in the 75 and 375 microg/kg per day groups, morphologically abnormal sperm were observed in the 375 microg/kg per day group. Furthermore, atrophic changes in the prostate and seminal vesicle and degenerative changes in the testis were observed in the 375 microg/kg per day group. Although the alpha 2u-globulin level was reduced in this assay using BPA and EE, further studies are necessary before this assay becomes a useful method for detecting endocrine-mediated effects.     

Reduction pneumoplasty for severe emphysema. Does the debate await a neat sentence?

The aim of this study is to review the literature regarding reduction pneumoplasty (RP) or lung volume reduction surgery in order to assess the state of the art of this topic. Reduction pneumoplasty is a palliative surgical therapy that is offered to selected patients with severe non-bullous emphysema not responding to maximized medical therapy. The use of staple excision or plication of the most destroyed target areas of the lung appeared to be more effective than laser ablation. Currently, a one-stage bilateral procedure is the standard of care although a unilateral reduction can be preferable in patients with asymmetric emphysema and/or if a staged bilateral treatment strategy is planned. Randomized studies have suggested that RP is superior to medical therapy including respiratory rehabilitation for improving subjective dyspnea, exercise capacity, respiratory function and quality of life for up to 1 year. In addition, few long-term studies have suggested that the improvements obtained with RP can be maintained for several years in properly selected patients. Although several issues still await a definitive answer, the available literature data and our current experience have clearly indicated that RP works well and is a safe and effective procedure for palliating symptoms and improving respiratory function in severely disabled emphysematous patients.     

Problem of uterine and ovarian cancer mass screening

We express the mass screening data of uterine cervical cancer, endometrial cancer, and ovarian cancer in Japan. The increase in cervical cancer mass screening rate, correlate well with decreasing mortality for uterine cancer, but mortality is re-increasing now. It is concern to increase of uterine cervical dysplasia and cervical cancer of young women. Then, we need to start the screening for more young women. The detect ratio of uterine corpus cancer is increasing now. Then, we need to change the object, and introduce new screening method for example, trans vaginal echogram. Ovarian cancer screening method is not establishment, but mortality rate in patients with ovarian cancer will be increase in future. Trans vaginal echogram is the better method for the screening. On the economical reason, we have a tendency the cancer screenings are neglected. It is important to watch the policy of health carefully.     

Long-lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam

Environmental stressors can substantially affect the adaptive response of rats to novelty in a sexually dimorphic manner. Gender-related differences are also observed in neurochemical and behavioural patterns of adult rats following prenatal exposure to diazepam (DZ). In the present study the behavioural reactivity to novelty is investigated in open field (OF) and in acoustic startle reflex (ASR) tests, in non handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male and female rats prenatally exposed to DZ. A single daily s.c. injection of DZ (1.5 mg/kg) over gestation days 14-20 decreases GABA/BDZ receptor function in both sexes, as shown by the decreased electrographic hippocampal response to DZ and the increased response to picrotoxin, after intra-locus coeruleus injection of the two compounds. In OF NH DZ-exposed males display a lower total distance travelled (TDT), a higher rearing frequency (RF) and a greater number of transitions in the centre of the arena (CNT) compared to NH rats prenatally exposed to vehicle. Conversely, NH DZ-exposed females show slight changes in TDT and RF and a greater reduction in CNT and in the amount of time spent in the centre of the arena (CAT). These effects are associated with an increase in the peak amplitude of the ASR in both sexes. Short-lasting handling slightly influences DZ-evoked effects in animals of both sexes. In DZ-exposed males long-lasting handling attenuates the reduction in TDT and the enhancement in RF, prevents the increase in CNT and reduces the peak amplitude of ASR. In DZ-exposed females, long-lasting handling increases TDT and RF, induces a lower avoidance of the centre of the arena, and does not modify the peak amplitude of ASR, when compared to controls. These findings indicate that prenatal exposure to DZ differently affects behavioural reactivity in adult male and female rats, and suggest that a long-lasting handling is able to attenuate some behavioural deficits induced by prenatal DZ exposure.     

Variations in Palatal Rugae in Near Term Fetuses from Untreated Jcl:ICR Mice

ABSTRACT The oral surface of the mouse palate has eight or nine pairs of transverse ridges, or rugae. Abnormalities in the pattern of palatal rugae have been reported in mutant mice and mice exposed to teratogens in utero. The purpose of this study was to describe control data of ruga variations for proper definition of "anomalous" ruga patterns. Jc1:ICR mice on gestation day 18 were killed, and the fetuses were fixed in Bouin's solution. Fetal palates were examined under a dissecting microscope. In total, 251 fetuses from 19 dams were observed. Among these fetuses 88% had one or more variations in the palatal rugae. Common variations were supernumerary anterior to the fourth ruga, division, and lateral bifurcation, and these were regarded as variations in the "normal" range. Variations rare in fetuses from untreated dams were shortness, fusion, cross, and supernumerary posterior to the fifth ruga, and these should be defined as "anomalous" ruga patterns in teratology experiments. Key words: mouse, palate, rugae, developmental toxicity test     

Effects of N-acetyl-L-cysteine on Teratogenicity of 5-Fluorouracil in Mice

ABSTRACT Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by N-acetyl-L-cysteine (NAC) andor phorone were evaluated in mice. Pregnant ICR mice were intraperitoneally injected with 25 mglkg of 5-FU on day 11 of gestation (vaginal plug = day 0). Pregnant mice were pretreated with NAC at dose levels of 80, 160, and 320 mg/kg injected intravenously 2 hours before dosing with 5-FU. Pregnant mice were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with 160 mg/kg and 320 mg/ kg of NAC decreased the incidence and severity of oligodactyly induced by 5-FU. There was little difference in maternal body weight gain, fetal mortality, and fetal weight between the 5-FU group and the 5-FU plus NAC groups. Pretreatment with phorone, a glutathione depleting agent, at dose levels of 160 and 320 mg/kg injected intraperitoneally, 4 hours before dosing with 5-FU, increased the incidence and severity of oligodactyly induced by 5-FU. Cotreatment with NAC at dose levels of 160 and 320 mg/kg decreased the incidence and severity of oligodactyly induced by 5-FU and 80 mg/kg of phorone. Cotreatment with NAC 160 mg/kg could not suppress the augmentative effect of phorone on 5-FU teratogenicity under the severe condition, that is, the excess amount of phorone such as 320 mg/kg. These results indicate that the teratogenicity of 5-FU is mitigated with NAC pretreatment, and also the level of endogenous glutathione is one of the factors which significantly affects teratogenicity of 5-FU.     

Quality of life assessments in women operated on by tension-free vaginal tape (TVT)

The aim of the study was to evaluate quality of life (QOL) prospectively in women who undergo tension-free vaginal tape (TVT) operation for stress urinary incontinence. Sixty-six women who completed QOL questionnaires and a 2-year follow-up examination were included. Improvement of health-related QOL was assessed by the Incontinence Impact Questionnaire-7 (IIQ-7), the Urogenital Distress Inventory-6 (UDI-6), and two questions regarding patient satisfaction and de novo urge incontinence. Prior to surgery, patients complained most of stress symptoms followed by physical activities and emotional health. Postoperatively IIQ-7 and UDI-6 as a whole and all seven domains improved significantly (p<0.001). Scores of IIQ-7, UDI-6, and seven domains did not differ between the adult and the elderly groups. Of the patients 88% were much satisfied or satisfied with surgical outcomes. Incidence of de novo urge incontinence was 12%. It is concluded that the TVT procedure significantly improved health-related quality of life.The authors listed above wrote this contribution on behalf of the Tension-free Vaginal Tape Trial GroupEditorial Comment: This study adds to the body of literature on the efficacy of the TVT procedure. Using quality of life instruments 88% of the patients were much satisfied or satisfied with surgical outcomes. Incidence of de novo urge incontinence was 12%. The biggest deficiency of the study was that follow-up was only available on 66 of 161 women     

Visualization of newly deposited tau in neurofibrillary tangles and neuropil threads

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.