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Background/Aim: This study aimed to evaluate the association between the change in peripheral eosinophil count during postoperative pelvic radiotherapy and gastrointestinal (GI) toxicities in patients with cervical cancer. Patients and Methods: The medical records of 163 patients with cervical cancer who underwent postoperative concurrent chemoradiotherapy between 2000 and 2016 were analyzed. Results: Among the peripheral blood cell counts, transient elevation of the eosinophil count was observed during radiotherapy. Of the 163 patients, 117 developed grade ≥2 diarrhea during radiotherapy, and 25 patients developed grade ≥2 late GI toxicities. In multivariate analysis, the maximum eosinophil count and age emerged as independent predictors of grade ≥2 acute diarrhea during radiotherapy, while bowel bag V40 Gy and age were predictive of grade ≥2 late GI toxicities. Conclusion: Early detection of transient elevation of eosinophil may facilitate early treatment of acute diarrhea during radiotherapy.

The deep inspiration breath hold (DIBH) technique is effective for heart dose reduction in patients with left-sided breast cancer. In deep breathing, some women breathe in thoracic respiration; and others, in abdominal respiration. This study evaluated differences in dose reduction in organs at risk (OAR) and reproducibilities of the target and OAR between thoracic DIBH (T-DIBH) and abdominal DIBH (A-DIBH). Fourteen patients with left-sided breast cancer who had planned to receive whole-breast irradiation were included. Computed tomography (CT) was performed in free breathing (FB), T-DIBH, and A-DIBH, and the dosimetric indexes of the target and OAR for three treatment plans were compared. In T-DIBH and A-DIBH, two series CTs were taken in each breathing method and the displacements of the target and heart were calculated. The averaged mean heart doses (MHDs) were 1.5 Gy and 1.6 Gy in T-DIBH and A-DIBH, respectively, significantly lower than 2.7 Gy in FB (p

Purpose To evaluate whether MediQOL, which was developed as a care cosmetic for sensitive skin, causes a change in skin condition for subjects with dry skin requiring moisture retention. Subjects and methods This study includes 20 Japanese subjects with dry skin who required moisture retention, as identified by a dermatologist. The subjects used the novel MediQOL products twice a day for four consecutive weeks. A skin evaluation was performed by a dermatologist, and each subject completed a questionnaire prior to the study period and after two and four weeks of MediQOL use. Results After four weeks of MediQOL use, alleviation of skin dryness, redness, and itchiness was observed in the subjects. The water/oil content of the skin also improved during the study period. Conclusion Four weeks of MediQOL use resulted in the alleviation of skin dryness, redness, and itchiness and balanced the water/oil content of the skin. MediQOL is expected to be effective in improving the condition of various skin types, including oily, mixed, and sensitive skin as well as dry skin.

Background The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Patients and methods We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. Results The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. Conclusion SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.

Acetylcholine (ACh), a quaternary ammonium cation, is known as one of the itch inducer in atopic dermatitis (AD), an inflammatory skin disease with intense itching. Previous research has reported accumulation of ACh in lesional site of AD patients. Generally, ACh is metabolized by cholinesterase (ChE). Therefore, one of the causes of ACh accumulation may be the suppression of ChE activity. Increased levels of the multifunctional bioactive sphingolipid sphingosylphosphorylcholine (SPC) have also been detected in AD. Since SPC possesses a quaternary ammonium cation, like ACh, it is possible that SPC affects the activity of ChE catalyzing ACh metabolization. We investigated whether SPC influences the activity of ChE by performing enzymatic analysis of ChE in the presence of SPC. We found that SPC strongly suppressed acetylcholinesterase (AChE) activity, but the suppression of butyrylcholinesterase by SPC was quite low. The Michaelis constant (Km) of AChE in the presence of SPC increased, and the maximum velocity (Vmax) decreased, indicating that SPC acts as mixed-type inhibitor for AChE. The analysis of SPC analogs clarified the importance of both the quaternary ammonium cation and the carbon chain length of SPC for the AChE inhibitory effect and showed that SPC was unique in AChE inhibition among the sphingolipids in this study. These findings indicate a novel function of SPC on AChE inhibition. Thus, the inhibition activity of SPC may be a factor in the increase of ACh in AD.

The hanger reflex (HR) is an involuntary head rotation that occurs in response to a clothes hanger encircling the head and compressing the unilateral fronto-temporal area. Here, we developed an elliptical device to induce the HR and examined its utility for the treatment of cervical dystonia (CD). The study included 19 patients with rotational-type CD. The device was applied to each subject’s head for at least 30 min/day for 3 months. Severity scores on part 1 of the Toronto Western Spasmodic Torticollis Rating Scale were evaluated at baseline and after the 3-month trial. Mean scores without and with the device were significantly different both at baseline (16.6 vs. 14.7, respectively; P < 0.05) and after the trial (14.9 vs. 13.6, respectively; P < 0.05). This preliminary trial suggests that our device can improve abnormal head rotation in patients with CD.

The delineation of the molecular pathology underlying amyotrophic lateral sclerosis (ALS) is being hampered by the lack of suitable biomarkers. We have previously reported that bromocriptine upregulates the endogenous antioxidative factor, neuronal apoptosis inhibitory protein (NAIP), sustains motor function and slows disease progression in ALS patients, implying the NAIP’s implication in ALS. Here, we aimed to verify a correlation of NAIP level with disease progression in ALS patients. The amount of NAIP in mononuclear cells (MNC) from peripheral blood from ALS patients (n = 18) and the age matched healthy controls (n = 12) was validated by NAIP-Dot blotting. Notably, the MNC-NAIP level in ALS patients (0.62 ± 0.29 ng) was nearly half of that in the healthy controls (1.34 ± 0.61 ng, P = 0.0019). Furthermore, the MNC-NAIP level in ALS patients and their ALS Functional Rating Scale-Revised (ALSFRS-R) score were evaluated through 1 year. Regression analysis of the MNC-NAIP vs ALSFRS-R indicated that a higher amount of MNC-NAIP was associated with a smaller change in ALSFRS-R at 12 months (R2 = 0.799; P = 0.016), suggesting that a progressive increment of the MNC-NAIP led to slower ALS progression. Our present report implies that NAIP will have broad implications for ALS symptoms as a risk factor and a promising prognostic biomarker.

The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

Background The Lachman test is clinically considered to be a reliable physical examination for anterior cruciate ligament (ACL) deficiency. However, the test involves subjective judgement of differences in tibial translation and endpoint quality. An auscultation system has been developed to allow assessment of the Lachman test. The knee joint sound during the Lachman test was analyzed using fast Fourier transformation. The purpose of the present study was to quantitatively evaluate knee joint sounds in healthy and ACL-deficient human knees. Methods Sixty healthy volunteers and 24 patients with ACL injury were examined. The Lachman test with joint auscultation was evaluated using a microphone. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of the Lachman sound, the peak sound (Lachman peak sound) as the maximum relative amplitude (acoustic pressure) and its frequency were used. Results In healthy volunteers, the mean Lachman peak sound of intact knees was 100.6 Hz in frequency and −45 dB in acoustic pressure. Moreover, a sex difference was found in the frequency of the Lachman peak sound. In patients with ACL injury, the frequency of the Lachman peak sound of the ACL-deficient knees was widely dispersed. In the ACL-deficient knees, the mean Lachman peak sound was 306.8 Hz in frequency and −63.1 dB in acoustic pressure. If the reference range was set at the frequency of the healthy volunteer Lachman peak sound, the sensitivity, specificity, positive predictive value, and negative predictive value were 83.3%, 95.6%, 95.2%, and 85.2%, respectively. Conclusion Knee joint auscultation during the Lachman test was capable of judging ACL deficiency on the basis of objective data. In particular, the frequency of the Lachman peak sound was able to assess ACL condition.

Antioxidant defense is crucial in restoring cellular redox homeostasis. Recent findings have suggested that oxidative stress plays pivotal roles in the pathogenesis of many neurodegenerative diseases. Thus, an anti-oxidative stress remedy might be a promising means for the treatment of such disorders. In this study, we employed a novel ligand-based virtual screening system and identified a novel small molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6-trimethylphenoxy) acetamide (CPN-9), which selectively suppressed oxidative stress-induced cell death in a cell-type-independent manner. CPN-9 upregulates NF-E2-related factor 2 (Nrf2), a key transcriptional regulator of the expression of phase II detoxification enzymes and antioxidant proteins, and Nrf2-regulated factors such as heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunit (GCLM). The CPN-9-mediated upregulation of HO-1, NQO1, and GCLM was abolished by Nrf2 knockdown. Moreover, the antioxidant N-acetylcysteine reduced the protective effect of CPN-9 against oxidative stress-induced cell death with concomitant diminishing of Nrf2 nuclear translocation. These results indicate that CPN-9 exerts its activity via the reactive oxygen species-dependent activation of the Nrf2 signaling pathway in cultured cells. It is noteworthy that the postonset systemic administration of CPN-9 to a transgenic ALS mouse model carrying the H46R mutation in the human Cu/Zn superoxide dismutase (SOD1) gene sustained motor functions and delayed disease progression after onset. Collectively, CPN-9 is a novel Nrf2 activator and a neuroprotective candidate for the treatment of neurodegenerative diseases, including ALS.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by a selective loss of upper and lower motor neurons. Since oxidative stress plays a crucial role in the progression of motor neuron loss observed in ALS, anti-oxidative agents could be an important therapeutic means for the ALS treatment. We have previously developed a drug screening system allowing the identification of small chemical compounds that upregulate endogenous neuronal apoptosis inhibitory protein (NAIP), an oxidative stress-induced cell death suppressor. Using this system, we identified the dopamine D2 receptor agonist bromocriptine (BRC) as one of NAIP-upregulating compounds. In this study, to prove the efficacy of BRC in ALS, we conducted a set of preclinical studies using a transgenic ALS mouse model carrying the H46R mutation in the human Cu/Zn superoxide dismutase (SOD1) gene ALS(SOD1(H46R)) by the post-onset administration of BRC. ALS(SOD1(H46R)) mice receiving BRC showed sustained motor functions and modest prolonged survival after onset. Further, BRC treatment delayed anterior horn cell loss, and reduced the number of reactive astrocytes and the level of inflammatory factors such as inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α in the spinal cord of late symptomatic mice. In vitro study showed the reduced level of extracellular TNF-α after lipopolysaccharide (LPS) exposure in BRC-treated mouse astrocytes. BRC-treated ALS(SOD1(H46R)) mice also showed a reduced level of oxidative damage in the spinal cord. Notably, BRC treatment resulted in an upregulation of anti-oxidative stress genes, activating transcription factor 3 (ATF3) and heme oxygenase-1 (HO-1), and the generation of a glutathione (GSH) in SH-SY5Y cultured neuronal cells in a dopamine receptor-independent manner. These results imply that BRC protects motor neurons from the oxidative injury via suppression of astrogliosis in the spinal cord of ALS(SOD1(H46R)) mice. Thus, BRC might be a promising therapeutic agent for the treatment of ALS.

Purpose.To compare mid-term outcomes of hemi-resurfacing arthroplasty (HRA) and total resurfacing arthroplasty (TRA).Methods.Seven men and 5 women (16 hips) aged 33 to 72 (mean, 50) years underwent HRA, whereas 7 men and 3 women (16 hips) aged 23 to 52 (mean, 40) years underwent metal-on-metal TRA; all were for osteonecrosis of the femoral head. In the HRA and TRA groups respectively, 10 and 8 hips were steroid-induced, whereas 6 and 8 hips were related to alcohol abuse. Surgery for 12 and 4 hips entailed the posterolateral approach, whereas 4 and 12 hips entailed the Hardinge approach. Usually, HRA was performed for early stages of the disease, and TRA for more advanced stages. 12 and 6 hips were classified as JOA stages 1 to 3A, whereas 4 and 10 hips as stages 3B to 4. All the hips were JOA types C1 or C2.Results.In the HRA and TRA groups respectively, the mean follow-up period were 6.5 and 5.5 years. The mean total JOA hip scores were 57 and 54 preoperatively, 93 and 97 at one year, and 84 and 96 at the final follow-up (pConclusion.TRA were superior to HRA in terms of pain relief and implant survival, even though the former procedure was used for more advanced cases.

The aim of Neuromodulation is the elimination of dysfunction or chronic discomfort related to neurological disorders by modulating the neural activity in specific parts of the central nervous system (Holsheimer, Neuromodulation 1(2) (1998) 57–61). Therefore, it is the treatable method for many symptom of various disease. Neuromodulation for movement disorder are DBS (Deep Brain Stimulation), ITB (Intrathecal Baclofen) and SCS (Spinal Cord Stimulation) commonly. Each of them improves not only motor dysfunction but also complicated symptoms. This accessory effects leads to further improvement of motor function. I will talk about following three cases in this symposium Improvement effect of DBS on sleep disorder of Parkinson’s disease SCS for intractable pain improves deep sensation, lower limb blood flow and mood disorder. Pain relief effect of ITB for CRPS. Recently, many pain physician have been discussing about central dysfunctional pain like CRPS. Chronic migraine is another well-known intractable disease attributable to the same mechanism with prevalence of 1.4–2.2% in Japan. Neuromodulation can possibly improve the activity of daily life of such patients. I will refer to Neuromodulation for headaches, mainly ONS (Occipital Nerve Stimulation).

Objective: To assess current trends in laparoscopic surgery, involving trocar insertion and wound closure.Design: Postquestionnaire survey.Setting: A consortium of 64 hospitals belonging to the Japanese Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE).Patient(s): NoneIntervention(s): None.Main outcome, Measure(s): Common clinical practices.Result(s): To assess procedural safety, the author issued a multicenter questionnaire directed at expert gynecologic laparoscopists authorized by the JSGOE. We received 64 completed surveys (a 59% response). Acknowledged differences in trochar insertion and wound closure, as in previous reports, were associated with rare intraoperative complications, such as rupture of larger blood vessels and intestines, trocar site bleeding/infection, and port-site hernia. The questionnaire also revealed strategies for prevention, formulated by those having experienced these complications.Conclusion(s): Laparoscopic surgical complications are largely attributable to trocar insertion. The body of preventive measures contributed by respondents to our questionnaire is therefore worthy of note, in order to increase the relative safety of this procedure.

妊娠中および帝王切開術直後に発生した癒着性イレウスに対して，大建中湯エキスを服用することにより，保存的に加療できた症例を経験した。症例は29歳女性。15歳の時に小腸軸捻転にて開腹歴あり。妊娠11週に癒着性イレウスを発症したため，大建中湯を投与したところ，大量の下痢便を認め症状は軽快。その後，胎児ジストレスにて36週に緊急帝王切開を施行。腹壁前面に小腸の強固な癒着を認めた。術後4日目に術後癒着性イレウスの診断にて，大建中湯を経口投与した。6日目に，軟状便および排ガスを認め，9日目には経口摂取を開始。その後は異常なく25日目に退院した。妊婦の高齢化に伴い，イレウス合併妊娠の報告が数多く認められる。妊娠中は母子ともに，重篤化しやすく外科的処置が必要となることが多いが，妊娠中や出産時に発生した癒着性イレウスに対して，大建中湯を用いることにより，保存的に改善する症例もあると考えられる。

Laparoscopic adenomyomectomies are performed in women with localized uterine adenomyosis with desired fertility. Both monopolar electric knives and Harmonic Scalpels® have been widely used in laparoscopic procedures; however, resection is not always easy, because both adenomyomatic and normal myometrial tissue develop heat degeneration with these devices, and the interface between abnormal and normal tissue is unclear. Here we report a successful adenomyomectomy using a cold knife (Endoscalpel®) following use of a Harmonic Scalpel®. The interface became clearer and the adenomyomatic lesion was resected.

Herein we report a clinical case involving trans-cervical resection (TCR) of a submucosal myoma protruding into the cervix with a stalk connected to the uterine cavity through the internal os. Before performing TCR, there was concern that leakage of fluid from the cervix would obscure the operative field. In this case, we chose TCR and successfully treated the submucosal myoma protruding into the cervix. TCR is an extremely effective procedure in terms of reliable homeostasis and diminishing the remaining tumor and stalk.

Neuronal apoptosis inhibitory protein (NAIP/BIRC1), the inhibitor of apoptosis protein (IAP) family member, suppresses neuronal cell death induced by a variety of insults, including cell death from ischemia and stroke. The goal of the present study was to develop an efficient method for identification of compounds with the ability to upregulate endogenous NAIP and to determine the effects on these compounds on the cellular response to ischemia. A novel NAIP-enzyme-linked immunosorbent assay (ELISA)-based in vitro drug-screening system is established. Use of this system identified an antagonist of dopamine D4 receptor, termed L-745,870, with a potent NAIP upregulatory effect. L-745,870-mediated NAIP upregulation in neuronal and nonneuronal cultured cells resulted in decreased vulnerability to oxidative stress-induced apoptosis. Reducing NAIP expression via RNA interference techniques resulted in prevention of L-745,870-mediated protection from oxidative stress. Further, systemic administration of L-745,870 attenuated ischemia-induced damage of the hippocampal CA1 neurons and upregulated NAIP expression in the rescued hippocampal CA1 neurons in a gerbil model. These data suggest that the NAIP upregulating compound, L-745,870, has therapeutic potential in acute ischemic disorders and that our NAIP-ELISA-based drug screening may facilitate the discovery of novel neuroprotective compounds.

We report the data on concurrent multiple point adsorption of two oppositely charged species of “target molecules” (aluminum ions and 1,3,6,8-pyrenetetrasulfonic sodium salt (Py-4)) by a polyampholyte gel of N-isopropylacrylamide (NIPA, 6 M) with methacrylic acid (MAA, 80 mM) and methacrylamidopropyl trimethylammonium chloride (MAPTAC, 80 mM). The goal of this study is to test the mutual frustrations created by adsorption of one species on the adsorption of the other. Understanding these frustrations is an important step toward elucidating the memory of conformations in heteropolymer systems. We found that in the absence of aluminum, the adsorption of Py-4 was suppressed by gel collapse, presumably because of an increase in MAA/MAPTAC ionic pairs that prevents the formation of potential adsorbing centers. Adding a moderate amount of aluminum significantly enhances adsorption of Py-4 by the collapsed gel, indicating that aluminum ions compete for bonds with MAA and help release vacant MAPTAC centers. Final...

The preventive effect of estrogen on Alzheimer's disease (AD) has become clear with epidemiological data. Therapeutic effects of estrogen have not yet been established. In this presentation, we report our new basic and clinical data. The estrogen receptor, (ER)alpha, and ERbeta mRNA were investigated in rat brain. Estradiol-17beta (E(2)) treatment following OVX reduced the levels of ERalpha mRNA in the hypothalamus. In the substantia innominata (SI), the number of choline acetyltransferase immunoreacive cells increased significantly in the estrogen treatment rat. The neurons in SI projecting to the forebrain cortex contained ERalpha. Increasing amounts of intracellular calcium, peroxidation, and apoptosis with amyloid beta were suppressed in neuronal cells from rat pheochromocytoma (PC12) cells with E(2). ERalpha cDNA transfected PC 12 cells elaborated more neurite-like processes with E(2). In clinics, we are currently preparing vaginal progesterone tablets, which essentially may concentrate in the endometrium to prevent endometrial cancer, with few general circulation of progesterone inviting less depression. The therapeutic effects of cyclic estrogen, such as its preventive effect, are suggested in these studies, at least on mild AD.

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP) and NF-E2-related factor 2 (Nrf2) which governed glutathione (GSH)-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1-100 µg/kg/day) WN1316 in ALS(SOD1(H46R)) and ALS(SOD1(G93A)) mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris). Thus, WN1316 would be a novel therapeutic agent for ALS.

Matsumoto, Keitaro, Kengo Ishihara, Kazunori Tanaka, Kazuo Inoue, and Tohru Fushiki. An adjustable-current swimming pool for the evaluation of endurance capacity of mice. J. Appl. Physiol. 81(4): 1843–1849, 1996.—A new forced-swimming apparatus for determining maximum swimming time in mice was devised for use in the evaluation of the endurance capacity of Std ddY and CDF1 mice after various diet and drug treatments. With the apparatus, a water current is generated by circulating water with a pump in a swimming pool. A spout and suction slit were contrived to generate a constant current while the strength of the current is regulated by a valve. The decrease in the leg-kicking intervals of mice accompanying the increase in the current speed confirmed that the workload is adjustable by regulation of the current speed. Compared with the number of forelimb strokes, that of the hindlimb kicks was greater. The swimming time until fatigue was observed to decrease with increasing current speed in the two strains of mice. As biochemical indexes, the blood lactate and muscle glycogen levels corroborated the correlation between current speed and increase in workload. These results indicate that the apparatus employed in the present study is suitable for the evaluation of the endurance capacity of mice and that it is useful for detecting the effects of dietary differences and drug pretreatments on this capacity.

The antioxidant activities of ten thiobisphenols were evaluated by an oxygen-absorption method at 60°C in tetralin and determination of peroxide values at 160°C in paraffin. For the 4,4′-thiobisphenols, alkyl groupsortho to the phenolic hydroxyl groups increased the induction period compared to that of other thiobisphenols for both oxidation of tetralin and paraffin. The data on electrochemical oxidation potentials that were determined by linear-sweep voltammetry and the13C nuclear magnetic resonance chemical shifts (δ) of these compounds were associated with antioxidant activities. In particular, the activities exhibited during the induction period closely correlated with the13C chemical shifts of ipso-carbon of the OH substituent.

In order to clarify the effects of estrogen on cholinergic basal forebrain neurons, a cholinergic neuron in the diagonal band nucleus of the female fetal rat was implanted into the anterior eye chamber of the female adult rat. Some host rats were treated with 2mg estradiol valerate (E2v) injected every 3 days after ovariectomy while others were not 2 and 4 weeks after transplantation, the growth of cholinergic neurons in the graft was studied using acethylcholinesterase (AChE) histochemistry. At 2 weeks after transplantation, AChE positive neurons and fibers were densely distributed in the grafts of E2v treated rats. Also in grafts without E2v treatment, AChE positive neurons and fibers were found in all the grafts although their density was low. At 4 weeks, AChE staining was dense staining observed in both groups. These results indicate that neurotrophic effect of estrogen on the cholinergic basal forebrain neurons.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. It has been shown that oxidative stress plays a pivotal role in the progression of this motor neuron loss. We have previously reported that L-745,870, a dopamine D4 receptor antagonist, selectively inhibits oxidative stress-induced cell death in vitro and exerts a potent neuroprotective effect against ischemia-induced neural cell damage in gerbil. To investigate the efficacy of L-745,870 in the treatment of ALS, we here conducted a chronic administration of L-745,870 to transgenic mice expressing a mutated form of human superoxide dismutase gene (SOD1(H46R)); a mouse model of familial ALS, and assessed whether the mice benefit from this treatment. The pre-onset administration of L-745,870 significantly delayed the onset of motor deficits, slowed the disease progression, and extended a life span in transgenic mice. These animals showed a delayed loss of anterior horn cells in the spinal cord concomitant with a reduced level of microglial activation at a late symptomatic stage. Further, the post-onset administration of L-745,870 to the SOD1(H46R) transgenic mice remarkably slowed the disease progression and extended their life spans. Taken together, our findings in a rodent model of ALS may have implication that L-745,870 is a possible novel therapeutic means to the treatment of ALS.

Cognitive and psycho-physiological condition in patients with long-term domiciliary oxygen therapy (DOT) remains uncertain. A cross sectional analysis was performed to investigate the age-related changes in cognitive and psycho-physiologic functions in patients with chronic respiratory failure receiving long-term DOT. Two expert practitioners visited the patient's home and examined them for analysis of cognitive function, emotional status, physical activity and degree of dyspneic sensation. One hundred and thirty-five patients completed the study. Control data from a cohort of 718 community dwellers were also included in this study. Male patients had significantly higher rates of chronic obstructive pulmonary disease (71% vs 47%, p = 0.001), lower values of forced expiratory volume in one second (FEV1.0) % (49.7 +/- 10.3 [standard deviation, S.D.] vs 66.0 +/- 7.5% predicted, p = 0.002) and higher Borg score, an indicator of dyspneic sensation, during daily exercise (3.2 +/- 0.8 [S.D.] vs 1.4 +/- 0.6, p = 0.01) compared with female patients. Linear regression analysis based on mean Mini-Mental State Examination scores, an indicator of cognitive function, showed that age-related cognitive decline was more pronounced in female patients than in female controls (-0.524/year, R2 = 0.426 vs -0.120/year, R2 = 0.027, p < 0.0001), while there was no significant difference between male patients and male controls (-0.156/year, R2 = 0.054, vs -0.077/year, R2 = 0.016, p = 0.231). These results demonstrate that age-related cognitive decline is more exaggerated in female patients receiving long-term DOT which should be taken into consideration in caring for patients with chronic respiratory failure.

Objectives: Monocyte adhesion to endothelial cells is an important initial event at the onset of atherosclerosis. It is partially mediated by the expression of adhesion molecules on the endothelial cell surface. While estrogens inhibit the development of atherosclerosis, the effect of co-administered progestin remains controversial. We examined the effect of progestins on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. Methods: In HUVECs, mRNA expression of progesterone receptors (PRs) and androgen receptors (AR) was determined by RT-PCR. HUVECs were stimulated by interleukin-1β (IL-1β) for 24 h with or without various steroids, and then the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was semiquantified by ELISA. Results: In all preparations of HUVECs used in this study, RT-PCR confirmed mRNA expression of both isoforms of PR, PR-A and PR-B, as well as AR. Addition of progesterone (10−10–10−7 M) or dienogest (DNG) (10−10–10−8 M) did not affect IL-1β-stimulated ICAM-1 or VCAM-1 expression. In contrast, medroxyprogesterone acetate, norethindrone acetate and levonorgestrel (10−10–10−8 M) dose-dependently increased cell adhesion molecules. The progestin-induced increase was blocked by the concomitant addition of mifepristone, a PR antagonist, but not by hydroxyflutamide, an AR antagonist, indicating that the progestin stimulation was mediated predominantly via PR. Conclusions: These results suggest that DNG, unlike other synthetic progestins, lacks stimulation of cell adhesion molecules. For the prevention of atherosclerosis, estrogen in combination with DNG may be a suitable regimen in hormone replacement therapy in postmenopausal women.

3n a previous report, we demonstrated in vivo ameliorating effects of conjugated estrogen in women suffering from senile dementia-Alzheimer's type. To investigate the effects of estrogen on the growth of cholinergic neurons, the present study was performed using rat cholinergic tissue implanted into the anterior chamber of the eye. Fetal diagonal band tissue containing cholinergic neurons was grafted into the anterior eye chamber of adult female rats that had either been treated or not with 2 mg estradiol valerate injected every 3 days after oophrectomy. Two and four weeks after transplantation, the axonal and/or dendritic growth of cholinergic neurons in the graft was studied using acetylcholinesterase histochemistry. At both times, acetylcholinesterase positive processes were densely distributed in the grafts of estradiol valerate treated rats, while in rats without estradiol valerate treatment acetylcholinesterase positive reaction was essentially localized only on the cell bodies. These findings were more obvious at 2 weeks after transplantation than at 4 weeks. These results suggest that estrogen acts on cholinergic neurons as a growth factor.

The effects of a diet supplemented with branched-chain amino acids (BCAA; 4.8% or 6.2%) on BCAA catabolism and glycogen metabolism in rats were examined. Rats were fed a BCAA diet or control diet for 4 wk and part of the rats were subjected to exercise training during the experimental period. Feeding the BCAA diet increased serum BCAA concentrations and activity of the hepatic branched-chain alpha-keto acid dehydrogenase complex, the rate-limiting enzyme in the catabolism of BCAA, suggesting that dietary BCAA promotes BCAA catabolism. Although the serum glucose concentration and glycogen contents in the liver and gastrocnemius muscle of rested rats were not significantly affected by feeding of the BCAA diet, those in rats exhausted by acute exercise were 2-4-fold higher in rats fed the BCAA diet than in rats fed the control diet. The activity of pyruvate dehydrogenase complex in the liver and gastrocnemius muscle after acute exercise showed reverse trends; the complex activities (especially in liver) tended to be less in the BCAA diet group than in the control diet group. These results suggest that dietary BCAA spares glycogen stores in liver and skeletal muscle during exercise and that the decrease in pyruvate dehydrogenase complex activity in these tissues by dietary BCAA is involved in the mechanisms.

We report an experimental realization of a gel system in which frustrations exist and can be minimized, thus meeting two crucial criteria predicted to enable memory of conformations in polymers. The gels consist of a thermosensitive major monomer component and two minor components. One minor component is positively charged and will form complexes around negatively charged target molecules placed in solution. The complexes can be imprinted into the gel by then cross-linking the second minor component, which will form cross-links additional to those in the major polymer matrix. The complexes are destroyed and reformed upon swelling and reshrinking of the gels, showing that memorization has been achieved.

✓ The authors report a case of middle cranial fossa neurinoma arising from the left greater superficial petrosal nerve in a 21-year-old woman who presented with a left-sided otitis media that chronically recurred over a period of 5 years. On examination, the patient had a left-sided mild conductive hearing impairment and a slight disturbance in tear secretion on the left side, with sensory disturbance in the left palate. Three-dimensional computerized tomography scans clearly demonstrated the enlargement of the foramen lacerum and foramen ovale, and heavily T2-weighted magnetic resonance images revealed the tumor's location along with the course of the greater superficial petrosal nerve and its extension into the tympanic cavity. Following complete surgical excision of the tumor and tympanoplasty via a middle cranial fossa approach, the patient retained useful hearing without facial palsy.

In order to evaluate the endocrine-disrupting effects of the styrene oligomers in polystyrene, used in cups for instant noodles, we examined the effects of styrene monomer (SM), styrene dimers (SD: NSD-01, 08, 09) and styrene trimers (ST: NST-01, 02, 03) on the estrogen receptor (ER) binding assay, the androgen receptor (AR) binding assay, the proliferation of MCF-7 human breast cancer cells, the steroidogenesis in Leydig cells of rats and the uterotrophic assay of immature rats. SM, SD and ST did not significantly bind to ER or AR of rats, did not induce the proliferation of MCF-7 cells, did not inhibit testosterone production in Leydig cells of rats, and did not induce estrogen-like alteration in the uterus and vagina of immature female rats. Therefore, it appears that these SM, SD and ST have no endocrine-disrupting effects through ER, AR and steroidogenesis mechanisms.

In 22 cases of Behcet’s disease (43 eyes, one eye with corneal staphyloma being excluded) manifesting ocular symptoms in the complete form, abnormal changes in the amplitude of the early receptor potential (ERP) were noted at the first consultation in 51.2% of the eyes examined as compared with 53.3% with abnormal areal indices (∑A) of the oscillatory potential and 39.5% with abnormal amplitudes of the b-wave in the ERG. Almost the same detection rate of abnormalities as in the ∑A of the oscillatory potential was obtained with respect to the ERP amplitude. The ERP and the b-wave were either reduced in their amplitude or absent in accordance with the grade and duration of this disease. Relatively early disappearance of the oscillatory potential was also noted.