Reproductive Effects of Early Neonatal Exposure to Diethylstilbestrol or Tamoxifen in Rats

To evaluate the effects of potential estrogenic or anti-estrogenic compounds on reproduction, male and female Sprague-Dawley rats were injected subcutaneously with 50 μg/kg diethylstilbestrol (DES) or 20 mg/kg tamoxifen (TAM) from postnatal day 1 to 5. Growth, estrous cycle, locomotor activity, and reproductive function including masculine sexual behavior, sperm motion, and development of reproductive organs were examined. Decrease in body weight gain and abnormal estrous cycle, such as persistent estrous, or prolonged estrous cycle were observed following early neonatal exposure to DES or TAM, while there was no effect on locomotor activity evaluated in the open field in the DES-or TAM-treated group. A marked decrease in sperm motility was found in the TAM-treated group. Anatomical and histological alterations of reproductive organs were observed in male and female rats in the DES-treated group and in female rats in the TAM-treated group. Early neonatal exposure to DES or TAM affected the masculine sexual behavior, resulting in a marked decrease in the ability to copulate and in fertility. In matings of the DES-or TAM-treated rats and intact rats, none of the treated females copulated successfully, whereas approximately 30% of treated males showed normal fertility. These results suggested that early neonatal exposure to DES or TAM induced more marked reproductive dysfunction after puberty in females than in males.     

Efficacy of Ramelteon in Patients with Insomnia and Nocturia

Objectives: To study the efficacy of ramelteon for patients with insomnia and nocturia. Methods: Forty‐nine patients experiencing insomnia and two or more nocturnal voids were included. The degree of lower urinary tract symptoms and sleep disorders was evaluated using the International Prostate Symptom Score (IPSS), Pittsburg Sleep Quality Index (PSQI) 1 score, and frequency/volume chart (FVC). The patients were treated with ramelteon (8 mg) for four weeks and then reexamined by questionnaire and FVC to evaluate the therapeutic efficacies. Results: The mean IPSS score was 16.1 ± 6.9 at baseline and 12.4 ± 7.1 at four weeks. The subject scores for the number of nocturnal voids also decreased significantly from 3.3 ± 0.9 to 2.9 ± 1.0. In addition, PSQI scores improved significantly from 7.4 ± 2.9 to 5.4 ± 2.8. According to the FVC, the number of nocturnal voids decreased significantly from 3.1 ± 1.2 at baseline to 2.2 ± 1.1 at four weeks, and nighttime bladder capacity improved significantly from 181.4 ± 79.9 to 201.1 ± 93.7 mL. Conclusion: Ramelteon alleviated nocturia and disturbed sleep in patients with insomnia and nocturia and led to increased nighttime bladder capacity.     

Acidosis and raised norepinephrine levels are associated with exercise dyspnoea in idiopathic pulmonary fibrosis

Background and objective:   Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods:   Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results:   Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO₂ and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO₃^- levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (ΔBorg scale/Δminute ventilation) correlated with the pH slope (ΔpH/Δoxygen uptake) (before the break point: r  = −0.537, P  = 0.0022; r  = −0.886, P  < 0.0001, after the break point) and the NE slope (ΔNE/Δoxygen uptake) (before the break point: r  = 0.481, P  = 0.0075; R  = 0.784, P  < 0.0001, after the break point).
Conclusions:   In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.     

T-cell-dependent eosinophilia in the cerebrospinal fluid of the mouse infected with Angiostrongylus cantonensis

Eosinophilia of the cerebrospinal fluid (CSF) in permissive (rats) and non-permissive (mice) hosts infected with Angiostrongylus cantonensis, and the possible mechanism of the eosinophilia were studied. In three strains of thymic mice (ICR, ddY and BALB/c), the infection provoked a marked CSF eosinophilia starting at around day 12, reaching a peak level at day 20 and maintaining significantly high levels until day 35. In contrast, in athymic nude mice of BALB/c strain the infection failed to evoke this eosinophilia, suggesting T-cell dependence of murine CSF eosinophilia. Humoral antibodies did not correlate with the induction of eosinophilia. A time-course study of worm recovery in the mouse brains indicated a gradual but consistent reduction in worm burden in accordance with the rapid rise in CSF eosinophil levels. Bone marrow eosinophilia occurred in mice at day 5, which preceded CSF eosinophilia. Jirds, a permissive but less susceptible host, developed a CSF eosinophilia with a peak level at day 17, but which declined rapidly following the peak. Permissive rat hosts developed significant peripheral and bone marrow eosinophilia at day 35 but their CSF eosinophilia was markedly less prominent than that of mice and jirds. These data clearly indicate that there are distinct differences in the mechanism of eosinophilia and eosinophilia-inducing factors between permissive and non-permissive hosts.     

Experience of Staged Angioplasty to Avoid Hyperperfusion Syndrome for Carotid Artery Stenosis

Hyperperfusion syndrome (HPS) after carotid artery stenting (CAS) may cause hemorrhagic or ischemic events leading to serious sequelae. We previously reported the staged angioplasty (SAP) to prevent HPS. In the present study, we analyzed our treatment results of SAP to know its effectiveness and problems. The study included 43 patients scheduled for SAP in whom preoperative single photon emission computed tomography (SPECT) showed severely impaired cerebral blood flow (CBF). The analyzed subjects were 38 males and 4 females, mean age was 73 ± 8.5 years old. SAP was indicated for the patients whose CBF ratio in the affected/unaffected hemisphere (asymmetry index) was below 0.8, and cerebrovascular reactivity measured by acetazolamide challenge was below 10%. First, percutaneous transluminal angioplasty (PTA) was performed. If PTA was successful, CAS was performed 2 weeks later. If PTA was not successful due to inadequate dilatation or extensive dissection, a stent was placed. SPECT was performed immediately after PTA and CAS to confirm the presence or absence of hyperperfusion phenomenon (HPP) indicating radiologic hyperperfusion. In 39 of 43 patients (91%), SAP was successfully performed and HPP was not observed. On the other hand, in the other four patients (9%), immediate stent placement was added due to inadequate dilatations in three patients and vascular dissection in one. Among 43 candidates for SAP, 41 patients (95.4%) had favorable course, but one hemorrhagic and one ischemic complications were observed after PTA. SAP was a relatively simple procedure, and its clinical results seemed acceptable.