Three-Dimensional Vascular Architecture of the Dog Heart as Revealed by Injection Replica Scanning Electron Microscopy

The three-dimensional vascular architecture of the dog myocardium was investigated by means of injection replica scanning electron microscopy. Coronary arteries entered into myocardial wall at almost right angle. They repeated bicornal divisions and run toward endocardium. The arterioles and precapillary arterioles branched in bicornal, tricornal or multicornal fashions. These branches were arranged usually in a plane in short distances. Capillaries were arranged parallel to the myocardial cells and had many anastomotic channels. The branching of the capillaries was usually Y-, T-, H- or K-shape, and Y-shape was the most common. Many anastomotic channels between precapillary arterioles were recognized just under the endocardiurn, while same connections were very difficult to identify in the myocardial wall. Numerous venous capillaries joined together with postcapillary venules and collecting venules almost exclusively in a plane parallel to the capillary sheets. Junctional architecture of these capillaries and venules was usually fan-shaped, finger-shaped or feather-shaped in appearance. The postcapillary venules and collecting venules were oriented usually perpendicular to the muscle fiber or capillary direction. The orifices of Thebesian veins, arterio-luminal vessels and arterio-sinusoidal vessels were observed between ventricular trabeculae as small masses of injected resin. The number of these orifices were more abundant in the right ventricular wall than in the left

Evaluation of the Subchronic Toxicity of Dietary Administered Equisetum arvense in F344 Rats

Equisetum arvense, commonly known as the field horsetail, has potential as a new functional food ingredient. However, little information is available on its side effects, and the general toxicity of Equisetum arvense has yet to be examined in detail. In the present study, we evaluated the influence of administration in diet at doses of 0, 0.3, 1 and 3% for 13 weeks in male and female F344 rats. No toxicity was detected with reference to clinical signs, body weight, urinalysis, hematology and serum biochemistry data and organ weights. Microscopic examination revealed no histopathological lesions associated with treatment. In conclusion, the no-observed-adverse-effect level (NOAEL) for Equisetum arvense was determined to be greater than 3% in both sexes of F344 rat (males and females: >1.79 g/kg BW/day and >1.85 g/kg BW/day, respectively) under the conditions of the present study

Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y

<p>Abstract</p> <p>Background</p> <p>SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA), but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K) is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E), each of which show a different phenotype during RA-mediated differentiation.</p> <p>Findings</p> <p>SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF) for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells.</p> <p>Conclusion</p> <p>We identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.</p

Experimental Evaluation of Bretschneider's Solution for Myocardial Preservation in Cardiac Transplantation

Myocardial preservation by Bretschneider's solution (BR solution, Group I) with an intracellular like electrolyte and histidine buffer action was compared with EC-Bi solution (Group II) which has an extracellular like electrolyte and bicarbonate buffer action in the mongrel dogs. The PH and PCO2 of the effluent from the coronary sinus were maintained during myocardial ischemia for 3 hr but the lactate rose gradually in group I. The oxygen and lactate up-take ratio of the myocardium after re-perfusion was satisfactory and LV max dp/dt was also maintained at a high level in group I. Morphologically, myelin figure and mitochondrial deformation were more found in group II on electron microscopy. A donor heart preserved for 3 hr in cold BR solution was transplanted in the left thoracic cavity in four mongrel dogs by the technique of the heterotopic cardiac transplantation. Resuscitation of cardiac pulsation was smooth and maintenance of the systemic circulation after transplantation was possible in every case. From these findings, it might be concluded that myocardial preservation using cold BR solution was useful for cardiac transplantation

Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats

The purpose of this study was to examine whether perinatal exposure to two major environmental endocrine-disrupting chemicals, bisphenol A (BPA; 0.1 mg/kg/day orally) and nonylphenol [NP; 0.1 mg/kg/day (low dose) and 10 mg/kg/day (high dose) orally] daily from gestational day 3 to postnatal day 20 (transplacental and lactational exposures) would lead to behavioral alterations in the male offspring of F344 rats. Neither BPA nor NP exposure affected behavioral characteristics in an open-field test (8 weeks of age), in a measurement of spontaneous motor activity (12 weeks of age), or in an elevated plus-maze test (14 weeks of age). A passive avoidance test (13 weeks of age) showed that both BPA- and NP-treated offspring tended to delay entry into a dark compartment. An active avoidance test at 15 weeks of age revealed that BPA-treated offspring showed significantly fewer avoidance responses and low-dose NP-treated offspring exhibited slightly fewer avoidance responses. Furthermore, BPA-treated offspring significantly increased the number of failures to avoid electrical unconditioned stimuli within 5-sec electrical shock presentation compared with the control offspring. In a monoamine-disruption test using 5 mg/kg (intraperitoneal) tranylcypromine (Tcy), a monoamine oxidase inhibitor, both BPA-treated and low-dose NP-treated offspring at 22–24 weeks of age failed to show a significant increment in locomotion in response to Tcy, whereas control and high-dose NP-treated offspring significantly increased locomotion behavior after Tcy injection. In addition, when only saline was injected during a monoamine-disruption test, low-dose NP-treated offspring showed frequent rearing compared with the control offspring. The present results indicate that perinatal low-dose BPA or NP exposure irreversibly influenced the reception of fear-provoking stimuli (e.g., electrical shock), as well as monoaminergic neural pathways

Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease

Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations

Mechanistic Insight on the Formation of GaN:ZnO Solid Solution from Zn–Ga Layered Double Hydroxide Using Urea as the Nitriding Agent

A solid solution of GaN and ZnO (GaN:ZnO) is promising as a photocatalyst for visible light-driven overall water splitting to produce H2. However, several obstacles still exist in the conventional preparation procedure of GaN:ZnO. For example, the atomic distributions of Zn and Ga are non-uniform in GaN:ZnO when a mixture of the metal oxides, i.e., Ga2O3 and ZnO, is used as a precursor. In addition, GaN:ZnO is generally prepared under harmful NH3 flow for long durations at high temperatures. Here, a facile synthesis of GaN:ZnO with homogeneous atomic composition via a simple and safe procedure is reported. A layered double hydroxide (LDH) containing Zn2+ and Ga3+ was used to increase the uniformity of the atomic distributions of Zn and Ga in GaN:ZnO. We employed urea as a nitriding agent instead of gaseous NH3 to increase the safety of the reaction. Through the optimization of reaction conditions such as heattreatment temperature and content of urea, single-phase GaN:ZnO was successfully obtained. In addition, the nitridation mechanism using urea was investigated in detail. NH3 released from the thermal decomposition of urea did not directly nitride the LDH precursor. X-ray absorption and infrared spectroscopies revealed that Zn(CN2)-like intermediate species were generated at the middle temperature range and Ga–N bonds formed at high temperature along with dissociation of CO and CO2.This file includes Supporting Information.This work was supported by JSPS KAKENHI Grant Number JP16H06438, JP16H06441, JP17H05483, JP17H03392. This work was partly supported by the Center for Functional Nano Oxide at Hiroshima University. The synchrotron radiation experiments were performed at the BL01B1 beamline of SPring-8 with the approval of the Japan Synchrotron Radiation Research 32 Institute (JASRI) (Proposal No. 2017B1043 and 2018A1749)

Eating-related distress and need for nutritional support of families of advanced cancer patients: A nationwide survey of bereaved family members

Background: A number of advanced cancer patients are suffering from physical and psychosocial burdens because of cancer cachexia, and these burdens also greatly impact on their family members and relationships between patients and family members. It is necessary to consider the psychosocial impact of cancer cachexia on family members of advanced cancer patients. Methods: A cross-sectional anonymous nationwide survey was conducted involving 925 bereaved family members of cancer patients who had been admitted to 133 inpatient hospices throughout Japan. Results: A total of 702 bereaved family members returned the questionnaires (response rate, 75.9%). Concerning eating-related distress, 'I served what the patient wanted without consideration of calories and nutritional composition' was highest (75.1%), and 'I tried making many kinds of meals for the patient' and 'I was concerned about planning meals for the patient every day' followed (63.0% and 59.4%, respectively). The top 5 of the 19 items were categorized as 'fighting back'. Need for nutritional support was high (72.2%), and need for explanations about the reasons for anorexia and weight loss of patients was moderate (41.4%). Explanatory factor analysis of eating-related distress identified the following four domains: (factor 1) feeling that family members forced the patient to eat to avoid death, (factor 2) feeling that family members made great efforts to help the patient eat, (factor 3) feeling that eating was a cause of conflicts between the patient and family members, and (factor 4) feeling that correct information was insufficient. Results of multiple logistic regression analysis showed that spouse, fair/poor mental status, factors 1, and 4 were identified as independent determinants of major depression (odds ratio [OR] 3.27 [95% confidence interval (CI) 1.24-8.60], P=0.02; OR 4.50 [95% CI 2.46-8.25], P<0.001; OR 2.51 [95% CI 1.16-5.45], P=0.02; OR 2.33 [95% CI 1.13-4.80], P=0.02, respectively). Conclusions: A number of family members of advanced cancer patients experienced high levels of eating-related distress and had a need for nutritional support

Some Properties of Azuki Bean Mosaic Virus Isolated from Soybean Plants in Ibaraki Prefecture

Azuki bean mosaic virus (ABMV) was isolated from Glycine max showing mild mosaic and stunt on the leaves, collected in Ibaraki-Prefecture, in July, 1989. ABMV was transmitted by sap-inoculation to 8 species systemically and 14 species locally out of 33 species in 8 families and by aphids, Aulacorthum solani and Myzus persicae in a non-persistent manner.Seed transmission was recognized in 0.8% of the seeds of soybean cv."Iwate-wase-kurome" inoculated at seeding stage. The soybean plant infected with ABMV produced mottled seeds, which were radical- or saddle-like. The virus particles were flexuous rods, bout 750 nm in length. In ultrathin virus-infected tissues, cytoplasmic inclusions containing pinwheels and scrolls were observed in the cytoplasms. In DAS-ELISA, the virus reacted strongly with antiserum to ABMV. The weight of plants and seed of two soybean cv."Okuhara 1" and "Iwate-wase-kurome" inoculated with ABMV at the seedling stage was about 40～50% less than that of healthy plants.1989年7月、茨城県において軽いモザイクと委縮を生じたダイズからアズキモザイクウイルス（azuki bean mosaic virus,ABMV）を分離し、その諸症状を調べた。本ウイルスは汁液接種した8科33種の植物のうち3科8種が全身感染し、4科14種が局部病班または無病徴感染した。感染したダイズの種子はダイズモザイクウイルスと同様に放射または鞍掛状斑紋型の褐斑模様を発現した。また、幼苗感染したダイズ品種「岩手早生黒目」の種子で0.8％の伝染がも認められた。ジャガイモヒゲナガアブラムシとモモアカアブラムシで非永続的に伝搬した。本ウイルスの粒子は長さ約750nmのひも状であった。インゲンマメ病葉の細胞質内には束状に配列したウイルス粒子とpotyvirus特有の風車状および渦巻状の細胞質内封入体が観察された。本ウイルスはDAS-ELISAによりABMVに対する抗血清と反応陽性であった。ダイズの早生品種晩生品種ともに幼苗感染で収量が40～50％減少した。以上の結果から、本ウイルスはは既知のABMVと比較し、宿主範囲が広く、病原性のやや強い分離株とみなされた

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

To elucidate the effect of a large dose of di (2-ethylhexyl) phthalate (DEHP), a plasticizer and peroxisome proliferator-activated receptor-α (PPARα) agonist, on hepatic peroxisomes, we orally administered 1,000 mg/kg/day, once daily, to 3 male and 4 female cynomolgus monkeys for 28 days consecutively. Light-microscopic and electron microscopic examinations of the liver were carried out in conjunction with measurement of the hepatic fatty acid β-oxidation system (FAOS), carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (CPT) activities, which are peroxisomal and/or mitochondrial enzyme activities. Electron microscopically, enlargement of the mitochondria was observed with lamellar orientation of the cristae along the major axis. Although the number of peroxisomes showed a tendency to increase when compared with those in a biopsied specimen before treatment, no abnormality in morphology was observed. A slight increase in CPT activity was noted at termination. No changes were noted in hepatic FAOS or CAT activity. In conclusion, although repeated oral treatment of cynomolgus monkeys with a large dose of DEHP induced a subtle increase in the numbers of peroxisomes with slight enlargements of the mitochondria, this low-sensitivity response to peroxisome proliferators in cynomolgus monkeys was considered to be closer to the response in humans than that in rodents