Acyclic retinoid peretinoin reduces hemorrhage-associated brain injury in vitro and in vivo.

Peretinoin is an acyclic retinoid that stimulates retinoic acid receptors (NR1Bs) and produces therapeutic effects on hepatocellular cancer. We have previously shown that NR1B agonists such as Am80 and all trans-retinoic acid suppress pathogenic events in intracerebral hemorrhage. The present study addressed the actions of peretinoin and Am80 against cytotoxicity of a blood protease thrombin on cortico-striatal slice cultures obtained from neonatal rat brains. Application of 100 U/ml thrombin to the slice cultures for 72 h caused cell death in the cortical region and tissue shrinkage in the striatal region. Peretinoin (50 µM) and Am80 (1 µM) counteracted these cytotoxic effects of thrombin, and the effect of peretinoin and Am80 was blocked by LE540, an NR1B antagonist. A broad-spectrum kinase inhibitor K252a (3 µM) attenuated the cytoprotective effect of peretinoin in the cortical region, whereas a specific protein kinase A inhibitor KT5720 (1 µM) attenuated the protective effect of peretinoin in the cortical and the striatal regions. On the other hand, nuclear factor-κB (NF-κB) inhibitors such as pyrrolidine dithiocarbamate (50 µM) and Bay11-7082 (10 µM) prevented thrombin-induced shrinkage of the striatal region. Peretinoin and Am80 as well as Bay11-7082 blocked thrombin-induced nuclear translocation of NF-κB in striatal microglia and loss of striatal neurons. We also found that daily administration of peretinoin reduced histopathological injury and alleviated motor deficits in a mouse model of intracerebral hemorrhage. These results indicate that NR1B agonists including peretinoin may serve as a therapeutic option for hemorrhagic brain injury.

11C-Labeling of acyclic retinoid peretinoin by rapid C-[11C]methylation to disclose novel brain permeability and central nervous system activities hidden in antitumor agent.

Recently, retinoid actions on the central nervous system (CNS) have attracted considerable attention from the perspectives of brain disease diagnosis and drug development. Firstly, we successfully synthesized [11C]peretinoin esters (methyl, ethyl, and benzyl) using a Pd(0)-mediated rapid C-[11C]methylation of the corresponding stannyl precursors without geometrical isomerization in 82%, 66%, and 57% radiochemical yields (RCYs). Subsequent hydrolysis of the 11C-labeled ester produced [11C]peretinoin in 13 ± 8% RCY (n = 3). After pharmaceutical formulation, the resulting [11C]benzyl ester and [11C]peretinoin had high radiochemical purity (>99% each) and molar activities of 144 and 118 ± 49 GBq µmol-1 at total synthesis times of 31 min and 40 ± 3 min, respectively. Rat brain PET imaging for the [11C]ester revealed a unique time-radioactivity curve, suggesting the participation of the acid [11C]peretinoin for the brain permeability. However, the curve of the [11C]peretinoin rose steadily after a shorter time lag to reach 1.4 standardized uptake value (SUV) at 60 min. These various phenomena between the ester and acid became more pronounced in the monkey brain (SUV of > 3.0 at 90 min). With the opportunity to identify high brain uptake of [11C]peretinoin, we discovered CNS activities of a drug candidate called peretinoin, such as the induction of a stem-cell to neuronal cell differentiation and the suppression of neuronal damages.

Clear evidence of the carcinogenic potential of anthracene: A 2-year feeding study in rats and mice.

Anthracene is an environmental pollutant and its adverse effects on human health have long been a concern due to its persistence and bioaccumulation properties. However, there is insufficient evidence for its chronic toxicity, especially carcinogenicity, in either humans or experimental animals. In this study, its carcinogenicity and chronic toxicity were investigated in compliance with the OECD test guideline 451 (OECD TG 451) and Good Laboratory Practice Standards. Fifty male and 50 female F344 rats and 50 female BDF1 mice were administrated 0, 8000, 20000, or 50000 ppm anthracene in the diet for 104 weeks, and 50 male BDF1 mice were fed diets containing anthracene at 0, 3200, 8000, or 20000 ppm. Anthracene treatment had no adverse effect on either the survival rate or general condition of the rats or mice during the study period. Body weights were lower or tended to be lower in the anthracene-treated groups than in the control groups. Increased incidence of hepatocellular carcinoma and hepatocellular adenoma was observed in male rats and female mice. Renal cell carcinoma and renal cell adenoma, fibroadenoma in the mammary gland, and uterine endometrial stromal sarcoma were increased in female rats. Transitional cell carcinoma and transitional cell papilloma in the urinary bladder were also increased in male and female rats. In addition, several different pre-neoplastic lesions were increased in the anthracene-treated male and female rats and female mice. These results provide clear evidence that oral administration of anthracene for 104 weeks has a carcinogenic effect in male and female rats and female mice.

Pulmonary dust foci as rat pneumoconiosis lesion induced by titanium dioxide nanoparticles in 13-week inhalation study.

BACKGROUND: Most toxicological studies on titanium dioxide (TiO2) particles to date have concentrated on carcinogenicity and acute toxicity, with few studies focusing of pneumoconiosis, which is a variety of airspace and interstitial lung diseases caused by particle-laden macrophages. The present study examined rat pulmonary lesions associated with pneumoconiosis after inhalation exposure to TiO2 nanoparticles (NPs). METHODS: Male and female F344 rats were exposed to 6.3, 12.5, 25, or 50 mg/m3 anatase type TiO2 NPs for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. After the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. RESULTS: Numerous milky white spots were present in the lungs after exposure to 25 and 50 mg/m3 TiO2 NPs. Histopathological analysis revealed that the spots were alveolar lesions, characterized predominantly by the agglomeration of particle-laden macrophages and the presence of reactive alveolar epithelial type 2 cell (AEC2) hyperplasia. We defined this characteristic lesion as pulmonary dust foci (PDF). The PDF is an inflammatory niche, with decreased vascular endothelial cells in the interstitium, and proliferating AEC2 transformed into alveolar epithelial progenitor cells. In the present study, the AEC2 in the PDF had acquired DNA damage. Based on PDF induction, the lowest observed adverse effect concentration for pulmonary disorders in male and female rats was 12.5 mg/m3 and 6.3 mg/m3, respectively. The no observed adverse effect concentration for male rats was 6.3 mg/m3. There was a sex difference in lung lesion development, with females showing more pronounced lesion parameters than males. CONCLUSIONS: Inhalation exposure to TiO2 NPs caused PDF, an air-space lesion which is an alveolar inflammatory niche containing particle-laden macrophages and proliferating AEC2. These PDFs histopathologically resemble some pneumoconiosis lesions (pulmonary siderosis and hard metal pneumoconiosis) in workers and lung disease in smokers, suggesting that PDFs caused by exposure to TiO2 NPs in rats are an early pneumoconiosis lesion and may be a common alveolar reaction in mammals.

No evidence for carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model.

With the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. We performed a 26-week inhalation exposure studies of titanium dioxide nanoparticles (TiO2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) mice model for detecting carcinogenicity. Male and female rasH2 mice were exposed to 2, 8 or 32 mg/m3 of TiO2 NPs for 6 h/day, 5 days/week for 26 weeks. All tissues and blood were collected and subjected to biological and histopathological analyses. TiO2 NPs exposure induced deposition of particles in lungs in a dose-dependent manner in each exposure group. Exposure to TiO2 NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of alveolar epithelial type 2 cells was examined, and it was not increased by exposure to TiO2 NPs. This is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m3, which is considered to be a high concentration.

Improved diagnostic accuracy for pediatric obstructive sleep apnea using an out-of-center sleep test.

OBJECTIVE: Polysomnography (PSG) is considered the gold standard for diagnosing obstructive sleep apnea syndrome (OSA) in children. However, many hospitals do not carry out PSG evaluations, and use out-of-center sleep test (OCST) devices for diagnosis instead. The aim of this study was to confirm the reliability of OCSTs for the diagnosis of pediatric OSA. We also investigated the factors influencing diagnostic reliability of OCST for the severe OSA patients who should be treated earlier. METHODS: This was a retrospective study using the Ota Memorial Sleep Center database. We analyzed the data of children who underwent Type 4 OCST at home and Type 1 PSG in the sleep lab between April 2006 to April 2015. Cephalometric parameters and anthropometric findings such as enlarged tonsils were also evaluated. We compared the 3% oxygen desaturation index (ODI3%) measured by OCST with the apnea-hypopnea index (AHI) measured by PSG. We used Receiver Operator Curve (ROC) to calculate the optimal OCST- ODI3% value to diagnose PSG-AHI ≥10 per hour. In order to determine which factors increase the accuracy of OCST, we calculated the accuracy, sensitivity and specificity in regard to the predicted values using multiple logistic regression analysis. The Ethics Committee of Ota General Hospital approved the study (approval no. 21018). RESULTS: A total of 191 children were enrolled in this study. The study included 127 boys and 64 girls, with a mean age of 5.4 years (range: 3-8 years), BMI of 15.7 kg/m² (range: 11.5-35.7 kg/m²), PSG-AHI of 17.4 per hour (range: 0.3-89.8 per hour). The sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were 64.4%, 70.3% and 67.5%, respectively, to detect PSG-AHI ≥ 10 per hour for children with suspected OSA. Multivariable stepwise regression revealed that increases of sensitivity, specificity and accuracy with an OCST-ODI cutoff of 6.3 per hour were independently predicted by facial axis, which is cephalometric angle of 81° or less, and tonsil hypertrophy, which is Brodsky +3 or +4, showing increases to 73.3%, 71.3%, and 72.3%, respectively, whereas age, gender, body mass index, adenoid size and other cephalometric parameters were not significant predictors. CONCLUSION: The results of the statistical analyses suggest that it would be useful to add the assessment of tonsil size and facial axis as well as OCST to determine whether the threshold of PSG-AHI ≥ 10 per hour has been crossed.

[11C]NCGG401, a novel PET ligand for imaging of colony stimulating factor 1 receptors.

Colony-stimulating factor 1 receptors (CSF1R) are expressed exclusively on microglia in the central nervous system. The receptors regulate immune responses by controlling the survival and activity of microglia and are intricately involved in the pathophysiology of Alzheimer's disease. In this study, we developed [11C]NCGG401, a positron emission tomography (PET) ligand, targeting for CSF1R as an imaging biomarker for microglial pathophysiology in Alzheimer's disease. NCGG401 showed a high potency to inhibit human CSF1R kinase activity and a high binding affinity to human CSF1R. PET imaging with [11C]NCGG401 in healthy rats showed a good brain permeability. Furthermore, the specific binding component was determined by postmortem autoradiography in rat brain and human hippocampal sections. The knowledge of the characteristics of [11C]NCCC401, our initial CSF1R compound, we have obtained may be useful for further development and optimization of CSF1R radioligands for PET imaging of microglia.

Preoperative apnea-hypopnea index predicts increased postoperative intrathoracic pressure during sleep in patients who underwent endoscopic nasal surgery.

OBJECTIVE: Respiratory condition could worsen during sleep in patients with nasal packing following endoscopic nasal and sinus surgery (ESS) under general anesthesia. Recently, a noninvasive intrathoracic pressure estimation sensor was developed that uses photoplethysmographic pulse wave technology. The purpose of this study was to noninvasively evaluate the effect of bilateral nasal packing on respiration during sleep, using a photoplethysmographic pulse wave sensor in perioperative patients who underwent ESS under general anesthesia. METHODS: In this observational cross-sectional case-control study, estimated intrathoracic pressure and SpO2 were noninvasively measured during sleep with a wristband-type photoplethysmographic pulse wave sensor and a pulse oximeter in 43 patients with chronic sinusitis, nasal allergy, or septal deviation who underwent bilateral ESS under general anesthesia. Measurements were taken preoperatively, at postoperative day 1 (POD1) with bilateral nasal packing in place, and at POD5 after the nasal packing was removed. Based on the preoperative obstructive apnea-hypopnea index (AHI) score determined by overnight polysomnography, patients were classified into those with moderate to severe obstructive sleep apnea (OSA) (AHI ≥ 15/h) and those with mild or non-OSA (AHI ≤ 15/h). RESULTS: Significant changes were noted in estimated intrathoracic pressure, but not in SpO2 nadir, between time points. Estimated intrathoracic pressure decreased the most at POD1 with bilateral nasal packing in place in patients with OSA after ESS. Multivariate stepwise regression revealed the relative incidence of increased estimated intrathoracic pressure on POD1 was independently predicted by preoperative AHI, but not by age, body mass index, total nasal resistance, or preoperative SpO2 nadir. CONCLUSION: Use of the photoplethysmographic pulse wave sensor to noninvasively measure intrathoracic pressure detected changes in perioperative respiratory effort that pulse oximetry did not. Attention should be paid to the use of postoperative bilateral nasal packing in patients with moderate to severe OSA who undergo ESS under general anesthesia. Our results support the concept of using less, short-term, or no nasal packing after ESS.

A preoperative predictive study of advantages of airway changes after maxillomandibular advancement surgery using computational fluid dynamics analysis.

The purpose of this study was to develop a simulation approach for predicting maxillomandibular advancement-induced airway changes using computational fluid dynamics. Eight patients with jaw deformities who underwent maxillomandibular advancement and genioglossus advancement surgery were included in this study. Computed tomography scans and rhinomanometric readings were performed both preoperatively and postoperatively. Computational fluid dynamics models were created, and airflow simulations were performed using computational fluid dynamics software; the preferable number of computational mesh points was at least 10 million cells. The results for the right and left nares, including simulation and postoperative measurements, were qualitatively consistent, and surgery reduced airflow pressure loss. Geometry prediction simulation results were qualitatively consistent with the postoperative stereolithography data and postoperative simulation results. Simulations were performed with either the right or left naris blocked, and the predicted values were similar to those found clinically. In addition, geometry prediction simulation results were qualitatively consistent with the postoperative stereolithography data and postoperative simulation results. These findings suggest that geometry prediction simulation facilitates the preoperative prediction of the postoperative structural outcome.

Synthesis of L-[5-11 C]Leucine and L-α-[5-11 C]Methylleucine via Pd0 -mediated 11 C-Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging.

The efficient synthesis of L-[5-11 C]leucine and L-α-[5-11 C]methylleucine has been investigated using a continuous two-step sequence of rapid reactions consisting of Pd0 -mediated 11 C-methylation and microfluidic hydrogenation. The synthesis of L-[5-11 C]leucine and L-α-[5-11 C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15-38 % based on [11 C]CH3 I, radiochemical purity of 95-99 %, and chemical purity of 95-99 %. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L-[5-11 C]leucine or L-α-[5-11 C]methyl leucine in A431 tumor-bearing mice was performed. As a result, L-α-[5-11 C]methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L-α-[5-11 C]methylleucine in tumor tissue was high [12±3% injected dose/g tissue (%ID/g)].

Effect of position therapy and oral devices on sleep parameters in patients with obstructive sleep apnea.

PURPOSE: The purpose of this study was to elucidate the effect of a neck-worn position therapy device (PTD) and oral appliance (OA) on sleep parameters in patients with obstructive sleep apnea (OSA). METHODS: Patients with an apnea hypopnea index (AHI) of 5/h or more at baseline polysomnography were divided into a PTD group and an OA group randomly. All participants underwent a type 1 polysomnography for diagnosis and device-set outcome measurements. RESULTS: The PTD decreased the AHI from a mean of 24.2/h to 16.7/h, and the OA decreased the AHI from 20.8/h to 10.3/h. Snoring duration decreased from 31.1% to 16.9% in the PTD group, and from 41.2% to 30.7% in the OA group. There were no significant differences in these decreases between the two groups. The PTD decreased sleep-time percentage in the supine position from a mean of 67.4% to 4.5%, despite five patients who were unable to avoid the supine position. There were no significant differences in improvement in sleep efficiency, percentage of stage wake, stage N1, stage N2, and stage REM, and overall arousal and respiratory arousal indices between the two groups. However, the spontaneous arousal index worsened in the OA responders but remained unchanged in the PTD responders. Percentage of stage N3 sleep (%N3) was improved in the PTD responders but not in the OA responders. There were significant differences in spontaneous arousal index and %N3 between the two groups. CONCLUSION: PTDs are a potential treatment modality that does not disturb sleep in patients with OSA.

Computational fluid dynamics analysis for the preoperative prediction of airway changes after maxillomandibular advancement surgery.

Maxillomandibular advancement surgery is useful for treatment of sleep apnea. However, preoperative analysis and evaluation to facilitate decision-making regarding the direction and distance of maxillomandibular movement has primarily consisted of morphological analysis; physiological function is not evaluated. To improve preoperative prediction, this study used fluid simulation to investigate the characteristics and effects of airway changes associated with maxillomandibular movement. A one-dimensional model with general applicability was thus developed. Actual measurements of flow in patients were used in this fluid simulation, thus achieving an analysis closer to clinical conditions. The simulation results were qualitatively consistent with the actual measurements, which confirmed the usefulness of the simulation. In addition, the results of the one-dimensional model were within the error ranges of the actual measurements. The present results establish a foundation for using accumulating preoperative measurement data for more-precise prediction of postoperative outcomes.

Carcinogenicity of quinoline by drinking-water administration in rats and mice.

The carcinogenicity of quinoline was examined by administrating quinoline in the drinking water to groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of each sex. In rats, the doses of quinoline were 0, 200, 400, and 800 ppm for males and 0, 150, 300, and 600 ppm for females. In male rats, administration of quinoline was terminated at week 96 due to high mortality caused by tumors. There were significant increases of hepatocellular adenomas, hepatocellular carcinomas, hepatocellular adenomas and/or carcinomas (combined), and liver hemangiomas, hemangiosarcomas, hemangiomas and/or hemangiosarcomas (combined) in both male and female rats, and nasal esthesioneuroepitheliomas and sarcoma NOS (not otherwise specified) in males. In mice, doses of quinoline were 0, 150, 300 and 600 ppm for both males and females. Administration of quinoline was terminated at week 65 in males and at week 50 in females due to high mortality caused by tumors. There were marked increases of hemangiomas, hemangiosarcomas, and hemangiomas and/or hemangiosarcomas (combined) in the retroperitoneum, mesenterium, and liver in males, and in the retroperitoneum, mesenterium, peritoneum, and subcutis in females. Additionally, histiocytic sarcomas were statistically increased in the livers of female mice. Thus the present studies provided clear evidence of carcinogenic activity of quinoline administered in the drinking water in both rats and mice.

Nickel (II) pyrrocorphin: Enhanced binding ability in a highly reduced porphyrin complex.

Pyrrocorphin is an air-sensitive porphyrinoid with a highly reduced hexahydroporphyrin core. In contrast, pyrrolidine-fused pyrrocorphin (Pyr) obtained by successive 1,3-dipolar cycloaddition reactions of azomethine ylide to 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin is less air-sensitive. In order to reveal the effect of highly reduced porphyrin rings on the physicochemical properties of their metal complexes, we have prepared diamagnetic (S=0) Ni(II) complex Ni(II)(Pyr). The addition of excess pyridine (Py) to the toluene solution of Ni(II)(Pyr) yielded five-coordinate Ni(II)(Pyr)(Py), which was then completely converted to six-coordinate paramagnetic (S=1) Ni(II)(Pyr)(Py)2. The latter was characterized by UV-Vis, 1H NMR, CV, SQUID, and X-ray crystallography as well as DFT calculations. As compared with analogous complexes of porphyrin (Por), chlorin (Chl), and isobacteriochlorin (Iso) reported by Herges and co-workers (R. Herges et al., Inorg. Chem. 2015), Ni(II)(Pyr)(Py)2 has longer equatorial NiN and shorter axial NiN bonds. The CV study has shown a large decrease in HOMO-LUMO gap as the reduction of porphyrin ring proceeds, which has further been confirmed by UV-Vis and DFT calculation. Titration studies using 1H NMR and UV-Vis have shown that the first binding constant of pyridine toward Ni(II)(Pyr) is ca. 4 times as large as that of Ni(II)(Iso) and ca 230 times as large as that of Ni(II)(Por). Thus, we have concluded that the binding constant of pyridine to Ni(II) porphyrinoid increases by the following order: Por

Breast metastasis nine years after nephrectomy for renal cell carcinoma: A case report.

INTRODUCTION: The breast is a rare site for metastatic disease. We report a rare case of breast metastasis 9 years after nephrectomy for renal cell carcinoma (RCC) and include a review of the relevant literature. PRESENTATION OF CASE: An 82-year-old woman who developed an RCC underwent left nephrectomy in 2005. In October 2014, computed tomography (CT) revealed a mass of approximately 1cm in the lateral portion of the right breast. Breast ultrasonography (US) revealed a well-circumscribed, hypoechoic mass at the same site. Fine needle aspiration (FNA) was performed, but the sample was inadequate because it did not capture breast duct epithelial cells. In June 2015, follow-up US revealed enlargement of the mass, and core needle biopsy (CNB) was performed to confirm the diagnosis. Histological examination resulted in the diagnosis of breast metastasis from an RCC. The patient underwent surgery for partial mastectomy in November 2015. The patient was asymptomatic and free of detectable disease at 18-month follow-up. DISCUSSION: The diagnosis of breast metastasis by imaging examination is difficult, and the results of FNA examination are often inconclusive because of the absence of breast duct epithelial cells. Only 22 cases of breast metastasis from RCC have been described in the literature. In almost all the reported cases, lumpectomy or partial mastectomy was performed. CONCLUSION: It is important that histological diagnosis be determined by CNB and by other methods if the patient has a history of malignancy, and minimally invasive therapy should be performed in accordance with the prognosis.

Synthesis of PET probe O6-[(3-[11C]methyl)benzyl]guanine by Pd0-mediated rapid C-[11C]methylation toward imaging DNA repair protein O6-methylguanine-DNA methyltransferase in glioblastoma.

O6-Benzylguanine (O6-BG) is a substrate of O6-methylguanine-DNA methyltransferase (MGMT), which is involved in drug resistance of chemotherapy in the majority of glioblastoma multiform. For clinical diagnosis, it is hoped that the MGMT expression level could be determined by a noninvasive method to understand the detailed biological properties of MGMT-specific tumors. We synthesized 11C-labeled O6-[(3-methyl)benzyl]guanine ([11C]mMeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N9-(tert-butoxycarbonyl)-O6-[3-(tributylstannyl)benzyl]-N2-(trifluoroacetyl)guanine, was subjected to rapid C-[11C]methylation under [11C]CH3I/[Pd2(dba)3]/P(o-CH3C6H4)3/CuCl/K2CO3 in NMP, followed by quick deprotection with LiOH/H2O, giving [11C]mMeBG with total radioactivity of 1.34GBq and ≥99% radiochemical and chemical purities.

Comparison of diagnostic reliability of out-of-center sleep tests for obstructive sleep apnea between adults and children.

OBJECTIVES: Sleep studies for diagnosing obstructive sleep apnea (OSA) in children are laborious, expensive, inconvenient, and often not readily available. Out-of-center sleep test (OCST) devices have been studied for diagnosing OSA in adults, but few OCST studies have been done in children. The purpose of this study was to clarify the diagnostic reliability of OCST devices for children. METHODS: OCSTs using pulse oximetry and in-laboratory polysomnography (PSG) were performed separately in 686 adults and 119 children. For each apnea-hypopnea index (AHI) measured with PSG, accuracy, sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and positive/negative predictive value (PPV/NPV) were calculated for several cutoff values of 3% oxygen desaturation index (ODI) measured with OCST and analyzed. RESULTS: For definitive diagnosis in adults, the specificity, PLR, and PPV with a cutoff value of OCST-ODI 20/h were 98.3%, 29.26, and 97.4%, respectively, to detect PSG-AHI ≥20/h. Corresponding values with a cutoff value of OCST-ODI 15/h were 99%, 46.19, and 99.6% to detect an AHI ≥5/h. For exclusive diagnosis (screening) in adults, sensitivity, NLR, and NPV with a cutoff value of OCST-ODI 5/h were 96.4%, 0.068, and 91.9% to detect PSG-AHI <20/h and 84.1%, 0.21, and 45.9% to detect PSG-AHI <5/h. or definitive diagnosis in children, the corresponding values with a cutoff value of OCST-ODI 25/h were 98.6%, 16.0, and 90.9% to detect PSG-AHI ≥10/h and 98.1%, 8.281, and 90.9% for PSG-AHI ≥5/h. For exclusive diagnosis in children, with a cutoff of OCST-ODI 10/h, the corresponding values were 62.2%, 0.446, and 78.2% to detect PSG-AHI <10/h, 45.3%, 0.674, and 55.1% for PSG-AHI <5/h, and 34.0%, 0.908, and 10.3% for PSG-AHI <1/h. Statistical data of preschool children tended to be worse than those of school age children. CONCLUSIONS: In adults, OCST is reliable for the definitive diagnosis of AHI ≥20/h or ≥5/h and the exclusive diagnosis of AHI <20/h. However, in children, OCST should not be used alone for the definitive diagnosis or exclusive diagnosis.

Comparison of single or multiple intratracheal administration for pulmonary toxic responses of nickel oxide nanoparticles in rats.

OBJECTIVES: In this study, we focused on the qualitative and quantitative differences of the lung lesions induced by single or multiple intratracheal administration of nickel oxide nanoparticles (NiO). METHODS: Male rats were randomized into groups receiving intratracheal administrations in a single dose or two to four divided doses of 2 mg/kg/bw. Bronchoalveolar lavage fluid (BALF) analyses were performed at 3 and 28 d post-dose. Histopathological analyses were performed at 28 and 91 d post-dose. RESULTS: BALF analyses revealed pulmonary injury, inflammation, and increases in the parameters indicating processing the foreign material in all the NiO-treated groups. Histopathological analyses showed the phagocytosis of NiO by alveolar macrophages, degeneration and necrosis of alveolar macrophages, and inflammatory responses. In the comparison between single and multiple administrations, the trend for stronger toxicity effects was observed after multiple application at 3 d post-dose, while the obvious toxicity effects were also seen in case of single administration. No particular differences of lung lesions depending on the frequency of administration at 28 and 91 d post-dose were evident. CONCLUSION: Intratracheal NiO administration induced strong toxic response thoroughly even by single administration. Therefore, single administration was concluded to be applicable to assess the inhalation toxicity of nanomaterials and can be used in the screening test.

Spin-crossover between high-spin (S = 5/2) and low-spin (S = 1/2) states in six-coordinate iron(iii) porphyrin complexes having two pyridine-N oxide derivatives.

In contrast to the general tendency that six coordinate iron(iii) porphyrin complexes with neutral oxygen ligands adopt a high-spin state in a wide range of temperature, some complexes with substituted pyridine N-oxides have exhibited spin-crossover from high-spin to low-spin states with decreasing temperature both in solution and in the solid state.

Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIα.

The present study retrospectively analyzed the utility of topoisomerase IIα expression as a prognostic marker to predict the neoadjuvant chemotherapeutic response and survival among different breast cancer subtypes. The patients were subtyped and the expression of topoisomerase IIα was determined using immunohistochemistry. All patients (n=147) received an anthracycline-containing regimen preoperatively, and 139 (95%) patients also received docetaxel. Of the 147 patients, 25 (17%) were triple-negative and 20 (17%) were human epidermal growth factor receptor 2 (HER2)-positive. Among these subtypes, a significantly higher a rate (P<0.0001) and higher incidence of topoisomerase IIα expression (P=0.036) were observed compared with that in the hormone receptor-positive and HER2-negative breast cancer types. However, the expression of topoisomerase IIα revealed no correlation with the treatment response or survival in any of the subtypes. Therefore, these results indicated that the favorable response to anthracycline-containing chemotherapy among triple-negative and HER2-positive breast cancer was independent of the expression of topoisomerase IIα.