Effects of antihistamines,ebastine and terfenadine,on electrocardiogram in conscious dogs and cats

The purpose of this study was to evaluate the effects of ebastine and terfenadine on the electrocardiogram of conscious dogs and cats. In dogs, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the electrocardiographic QT interval and the corrected QT (QTc) interval on the seventh day, whereas the drug did not affect these parameters on the first day. Plasma concentrations of terfenadine and its active metabolite, fexofenadine, reached 306 and 8,541 ng/mL, respectively, on the seventh day. Ebastine at oral doses of 30 and 100 mg/kg once a day for 7 days was without effect on the QT and QTc intervals, whereas the drug slightly shortened the RR interval. On the seventh day following the dose of 100 mg/kg, plasma concentrations of ebastine and its active metabolite, carebastine, reached 36 and 1,939 ng/mL, respectively. In conscious cats, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the QT and QTc intervals, QRS duration, JT and the corrected JT intervals. Unexpectedly, terfenadine induced ventricular tachyarrhythmia and premature beats. On the other hand, ebastine at oral doses of 100 mg/kg once a day for 7 days was without effect on the electrocardiographic parameters in cats. These results suggest that the electrocardiographic changes indicative of the proarrhythmic potential of terfenadine can be evaluated in conscious dogs and especially in conscious cats by repeated oral administration, and that ebastine does not induce such changes. 58:209–217, 2003. © 2003 Wiley‐Liss, Inc.     

Transitional cell carcinoma of the ovary: Report of three cases

Background We investigated retrospectively the records and tissue samples of patients with primary ovarian transitional cell carcinoma to determine clinical and pathologic features. Methods The records of 3 patients with ovarian transitional cell carcinoma were reviewed using data from several imaging techniques: transvaginal ultrasound, computed tomography, and magnetic resonance imaging. We also determined levels of several tumor marker molecules; and the level of carbohydrate antigen 125 (CA 125), was examined by means of immunohistochemistry. Results The tumors of 2 patients were classified as pure trnasitional cell carcinoma; in the remaining patient, as predominantly transitional cell carcinoma. All tumors were bilateral, and 2 of the 3 tumors formed solid masses. Areas of irregular high intensity signals were seen in magnetic resonance images of the solid parts of the tumors. All 3 tumors tested positive for CA 125; histochemical expression was confined to the tumor cell membrane and/or the cytoplasm in all cases. The tumors of all 3 patients tested negative for carcinoembryonic antigen (CEA), and second-look laparotomies did not reveal any residual neoplasms in any of the patients. The patients have been in a disease-free state for 34, 42, and 14 months, respectively. Conclusion Our results suggest that transitional cell carcinomas tend to arise bilaterally and to form solid tumors. Magnetic resonance imaging was a useful diagnostic modality in these cases. Transitional cell carcinoma was characterized by the presence of CA 125 and the absence of CEA.     

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.     

Characterization of mouse Ire1 alpha: cloning, mRNA localization in the brain and functional analysis in a neural cell line

In yeast, an endoplasmic reticulum (ER)-associated protein, Ire1p, is believed to initiate the unfolded protein response (UPR), that is responsible for protein folding in the ER under stressed conditions. Two mammalian homologs of Ire1p have been identified, Ire1 alpha and Ire1 beta. We have previously reported that familial Alzheimer's disease linked presenilin-1 variants downregulate the signaling pathway of the UPR by affecting the phosphorylation of Ire1 alpha. In the present study, we cloned the mouse homolog of Ire1 alpha for generating genetically modified mice. Ire1 alpha was ubiquitously expressed in all mouse tissues examined, and was expressed preferentially in neuronal cells in mouse brain. This led us to investigate the effects of the downregulation of the UPR on the survival of neuronal cells under conditions of ER stress. Morphological and biochemical studies using a dominant-negative form of mouse Ire1 alpha have revealed that cell death caused by ER stress can be attributed to apoptosis, and that the downregulation of the UPR enhances the apoptotic process in the mouse neuroblastoma cell line, Neuro2a. Our results indicate that genetically modified mice such as transgenic mice with a dominant-negative form of Ire1 alpha might provide further understanding of the pathogenic mechanisms of Alzheimer's disease and other neurodegenerative disorders.     

Sensory Ataxic Guillain-Barré Syndrome with Dysgeusia after mRNA COVID-19 Vaccination

Guillain-Barré syndrome (GBS) has occasionally occurred in people who have received coronavirus disease 2019 (COVID-19) vaccines. Dysgeusia is rare symptom of GBS. We herein report a rare case of sensory ataxic GBS with dysgeusia just after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Although autoantibodies against glycolipids were not detected, immunotherapy with intravenous immunoglobulin and methylprednisolone pulse therapy effectively ameliorated the symptoms. Our report suggests that the COVID-19 vaccine may induce various clinical subtypes of GBS, including a rare variant with sensory ataxia and dysgeusia.     

Proteome analysis of human placentae: pre-eclampsia versus normal pregnancy

Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to obtain placental proteome maps. The identified protein spots (ca. 60% of the total) on the proteome maps included several pregnancy-related proteins (PRPs). Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to pre-eclampsia revealed three immunopositive spots that appeared to correspond to dynactin p-50, a protein related to cell turn-over. The rate of positivity for dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre-eclamptic women than in 58 normally pregnant women. These results indicate that dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.     

Impact of Dietitian-Led Nutrition Therapy of Food Order on 5-Year Glycemic Control in Outpatients with Type 2 Diabetes at Primary Care Clinic: Retrospective Cohort Study

The aim of this retrospective cohort study was to evaluate the effect of 5-year follow-up of dietitian-led medical nutrition therapy (eating vegetables before carbohydrates) on glycemic control in outpatients with type 2 diabetes (T2DM) at a primary care clinic. A total of 138 patients with dietitian-led medical nutrition therapy (intervention group) and 104 patients without dietitian-led nutrition therapy (control group) were compared for glycemic control, serum lipid, blood pressure, and diabetic complications for 5 years. Each patient in the intervention group received dietary education focused on food order (eating vegetables before carbohydrates) by dietitians. A significant improvement in HbA1c after 5 years in the intervention group [8.5 ± 1.7% (69 mmol/mol) to 7.6 ± 1.1% (59 mmol/mol), p < 0.001] was observed, whereas no change was observed in the control group [7.9 ± 1.2% (62 mmol/mol) to 8.0 ± 1.2% (63 mmol/mol)]. Dietary intake of protein, fat, carbohydrates, cholesterol, and salt in the intervention group demonstrated significant reduction, while the intake of dietary fiber significantly increased after the dietary education. Simple dietary education of ‘eating vegetables before carbohydrates’ presented by dietitians achieved good glycemic control after a 5-year period in outpatients with T2DM at primary care clinic.