Regional arterial stiffness in patients with type 2 diabetes and chronic kidney disease

Increased arterial stiffness is an independent predictor of death from cardiovascular disease, and aortic stiffness is more predictive than stiffness of other arterial regions. Because little is known about the effect of chronic kidney disease (CKD) on regional arterial stiffness, pulse wave velocity (PWV) of four different arterial segments was measured in patients who had type 2 diabetes with and without various stages of CKD. A total of 434 patients had type 2 diabetes, and there were 192 healthy control subjects who were comparable in age and gender. GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. The patients with diabetes were classified into CKD stages by the definition of the Kidney Disease Outcomes Quality Initiative guidelines. PWV was measured in the heart-femoral, heart-carotid, heart-brachial, and femoral-ankle segments simultaneously using an automatic pulse wave analyzer. PWV of each arterial region was increased in patients who had diabetes without kidney damage and was increased further in a stepwise manner with the advanced stages of CKD. The increase in PWV was greater in the heart-femoral and heart-carotid regions than in the heart-brachial and femoral-ankle segments. However, after adjustment for age, BP, and other confounding factors using a multiple regression model, decreased GFR was independently associated with increased PWV of the heart-femoral region but not with PWV of other arterial segments. In type 2 diabetes, CKD was associated with increased stiffness of arteries, particularly of the aorta. The cross-sectional result may explain the increased risk for cardiovascular disease in CKD, although longitudinal studies are needed to confirm it.     

Turbulent left-to-right shunt flow through the interatrial septum suggesting high left atrial pressure in patients with heart failure with preserved ejection fraction

Lutembacher’s syndrome is a combination of interatrial septal (IAS) defect or patent foramen ovale (PFO), associated with mitral stenosis. High left atrial (LA) pressure in mitral stenosis exaggerates left-to-right shunt in patients with interatrial communication. We present a case of heart failure with preserved ejection fraction. Echocardiography revealed normal left ventricular systolic function without mitral stenosis and turbulent left-to-right shunt through the IAS. The peak velocity of the shunt flow was 2.3 m/s and the estimated pressure gradient was 22 mmHg, indicating high LA pressure. The presence of turbulent left-to-right shunt through the IAS is helpful for detecting high LA pressure.     

Detectability of hypometabolic regions in mild Alzheimer disease: function of time after the injection of 2-[fluorine 18]-fluoro-2-deoxy-D-glucose

BACKGROUND AND PURPOSE: 2-[Fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has played an important role in detecting hypometabolic regions in the brains of patients with dementia. To our knowledge, the optimal imaging time for dementia has not been investigated. The aim of this study was to evaluate the sensitivity of the early scanning (ES) compared with late scanning (LS) for demonstrating decreased regional glucose metabolism in patients with Alzheimer disease (AD). METHODS: Twenty patients with mild AD (mean age +/- standard deviation, 64.8 +/- 5.2 years) and 20 age- and sex-matched healthy volunteers (age, 65.9 +/- 4.5 years) were underwent FDG PET. Their cerebral glucose metabolic images were obtained on ES at 30-42 minutes and LS at 60-72 minutes after the administration of FDG 185-346 MBq. We compared regional cerebral metabolic images in a voxel-by-voxel analysis with statistical parametric mapping between patients with AD and control subjects and evaluated the difference in the hypometabolic regions between the two scans. RESULTS: In the AD-to-healthy comparison, LS at the P < .001 level of significance showed more extensive and significant hypometabolic areas than did ES. CONCLUSION: These results indicate that LS is superior to ES in detecting hypometabolic regions in patients with AD. For patients with AD, emission scanning soon after the administration of FDG is probably not advised.     

The Efficacy and Renal Protective Effect of Tolvaptan in Chronic Kidney Disease Patients after Open-Heart Surgery

Purpose: Unlike loop diuretics, tolvaptan is reported to have a renal protective effect. The purpose of this study was to retrospectively assess the efficacy of tolvaptan administration in chronic kidney disease (CKD) patients following open-heart surgery.Methods: From February 2017 to August 2020, 75 patients with preoperative CKD stages IIIb–V were enrolled in this study and were divided into two groups: the control group (n = 30) and the tolvaptan group (n = 45). All patients routinely received conventional diuretics starting from postoperative day (POD) 1. Tolvaptan at 7.5–15 mg/day was administered if the patients had persistent fluid retention or poor response to conventional diuretics.Results: Tolvaptan administration was initiated at a mean of POD 2.9 ± 2.2, and the mean dosing period was 4.1 ± 3.0 days. The mean time to return to the preoperative body weight in the control and tolvaptan groups was similar. However, estimated glomerular filtration rate (eGFR) was significantly increased at the time when body weight reached the preoperative level and at discharge in the tolvaptan group than in the control group.Conclusion: This study demonstrated the renal protective effect of tolvaptan even in advanced CKD patients after open-heart surgery.     

Case of Hashimoto's encephalopathy with diffuse white matter lesions on diffusion-weighted MRI]

A 65-year-old woman was admitted to our hospital because of subacute deterioration of cognitive function. On admission, she presented with marked disorientation of time and place and inability to carry out commands. Mini-Mental State Examination score was 5/30. Although routine laboratory examinations including thyroid function, vitamin B1 and B12, serum syphilitic reaction, sIL-2 receptor level, titers of herpes simplex and zoster viruses, and HIV antibody were normal, titers of anti-thyroglobulin (TG) antibodies and thyroid peroxidase (TPO) antibodies were elevated. Cerebrospinal fluid showed normal findings. Brain MRI revealed diffuse high intensity in the white matter on diffusion- and T2-weighted images, mimicking leukoencephalopathy. We made a diagnosis of Hashimoto's encephalopathy, based on clinical features and high titers of anti-thyroid antibodies. Following administration of steroid hormone, her cognitive impairment gradually improved, associated with decrease of the white matter abnormality on MRI. Hashimoto's encephalopathy should be kept in mind in the differential diagnosis of subacute leukoencephalopathy with cognitive decline.     

Involvement of cathepsin B in the processing and secretion of interleukin‐1β in chromogranin A‐stimulated microglia

Cathepsin B (CB) is a cysteine lysosomal protease implicated in a number of inflammatory diseases. Although it is now evident that caspase‐1, an essential enzyme for maturation of interleukin‐1β (IL‐1β), can be activated through the inflammasome, there is still evidence suggesting the existence of lysosomal‐proinflammatory caspase pathways. In the present study, a marked induction of pro‐IL‐1β, its processing to the mature form and secretion were observed in the primary cultured microglia prepared from wild‐type mice after stimulation with chromogranin A (CGA). Although pro‐IL‐1β also markedly increased in microglia prepared from CB‐deficient mice, CB‐deficiency abrogated the pro‐IL‐1β processing. CA‐074Me, a specific inhibitor for CB, inhibited the pro‐IL‐1β maturation and its release from microglia. Furthermore, the caspase‐1 activation was also inhibited by CA‐074Me and E‐64d, a broad cysteine protease inhibitor. After treatment with CGA, CB was markedly induced at both protein and mRNA levels. The induced pro‐CB was rapidly processed to its mature form. The immunoreactivity for CB co‐localized with both that for caspase‐1 and the cleaved IL‐1β, in the acidic enlarged lysosomes. Inconsistent with these in vitro observations, the immunoreactivity for the cleaved IL‐1β was markedly observed in microglia of the hippocampus from aged wild‐type but not CB‐deficient mice. These observations strongly suggest that CB plays a key role in the pro‐IL‐1β maturationthrough the caspase‐1 activation in enlarged lysosomes ofCGA‐treated microglia. Therefore, either pharmacological or genetic inhibition of CB may provide therapeutic intervention in inflammation‐associated neurological diseases. © 2009 Wiley‐Liss, Inc.     

Simple and reproducible model of rat spinal cord injury induced by a controlled cortical impact device

Abstract

Consistently reproducible experimental trauma was inflicted on the rat spinal cord (L3-L4) employing a controlled cortical impact device. The spinal cord was injured with one of three sizes of chips; thick (3 mm diameter), medium (2 mm diameter), thin (1 mm diameter). Each chip was applied at ), 2 and 3 mm deformation depths. The correlations of the magnitude of the primary trauma were examined histopathologically. It was found that the extent and intensity of the trauma could be changed by altering the depth of deformation and the chip diameter at a fixed velocity of 4.6 m per sec. The injury caused by the 2 mm diameter chip at 0.5 mm deformation damaged one to two segments of the perifocal spinal cord. In the surviving animals, the histological changes could be classified as primary, secondary, and late phase changes, and finally the lesion became a cavity. This study reports the application of a controlled cortical impact device to morphological research on a spinal cord injury. We found that the injury by the 2 mm chip at 0.5 mm deformation was the most advantageous and reproducible model for further investigations. [Neurol Res 1999; 21: 313–323]