Ultrasound vasography evaluation of radial arterial grafts used for coronary arterial bypass surgery

OBJECTIVES: For coronary bypass surgery, radial arteries are often used as bypass grafts. Some of these arteries however, have arteriosclerotic lesions. We attempted to evaluate the relationship between arteriosclerosis and vasodilation. METHODS: Prior to bypass surgery, 20 patients underwent ultrasound vasography to determine the condition of their radial and brachial arteries. Flow-mediated dilation, which is the same as endothelium-dependent vasodilation, was measured in the brachial artery of the nondominant arm by reactive hyperemia after 5-minute forearm ischemia. Vasodilation after application of a sublingual glyceryl trinitrate spray was also measured. RESULTS: During surgery, 4 of 20 radial arteries demonstrated calcification, and 3 of the 4 could be used by removing the calcified part. However, the other artery, which had extensive calcification that could not be detected by ultrasound vasography, was discarded. The amount of vasodilation seen after the administration of sublingual glyceryl trinitrate had no correlation with calcified grafts. Calcified radial arteries demonstrated significantly poor brachial artery vasodilation by an endothelial-dependent vasodilation test. CONCLUSIONS: Calcification in radial arteries can thus only be evaluated by flow-mediated dilation.     

Proximal clipping and bypass between bilateral vertebral arteries using a radial arterial graft for the treatment of a dissecting aneurysm of the vertebral artery

Proximal clipping has been performed recently as the main surgical treatment for a dissecting aneurysm of the vertebral artery. When there is a contralateral vertebral artery of a smaller size with arteriosclerotic changes, some form of bypass to prevent cerebellar and brain stem infarction is needed in addition to proximal clipping. We treated a 50-year-old man with a ruptured dissecting aneurysm of the left vertebral artery and stenosis at the V3 segment of the right vertebral artery. The caliber of the right vertebral artery was smaller than the left. After an anastomosis between bilateral vetebral arteries using a radial arterial graft, dissecting aneurysm was clipped at the proximal portion of the aneurysm.     

A case of Gerstmann-Sträussler-Scheinker syndrome with the P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis

We describe the clinical features of a patient with Gerstmann-Sträussler-Scheinker syndrome with a mutation in the prion protein gene at codon 105 (GSS105) who presented with ataxia. Neurologic examination showed memory disturbance, dysarthria, extrapyramidal signs (bradykinesia and resting tremor) and ataxic gait without spasticity. Although GSS105 has been referred to as “spastic paraparesis-type GSS”, the patient did not show spastic paraparesis or pyramidal signs, even 11 years after the onset of symptoms. Thus, the spectrum of the GSS105 phenotype varies among patients and requires further clinicopathologic elucidation.     

Methotrexate reduces the levels of pentosidine and 8-hydroxy-deoxy guanosine in patients with rheumatoid arthritis

This study was performed to investigate whether methotrexate (MTX) affects the levels of oxidative stress markers, including pentosidine one of the glycation end products (AGEs) or 8-hydroxy-deoxy guanosine (8-OHdG). These stress markers represent DNA damage; 19 rheumatoid arthritis (RA) patients underwent MTX treatment. The levels of serum total, urinary total, urinary-free pentosidine and also urinary 8-OHdG, as well as clinical parameters, including disease activity scores for 28 joints (DAS28) were measured at baseline and at 3 and 6 months after the initial treatment with MTX. After the initial treatment with MTX, serum total and urinary total pentosidine levels were reduced at 6 months, and urinary-free pentosidine levels were reduced at 3 and 6 months. Urinary 8-OHdG levels also were significantly reduced at 6 months after the initial treatment with MTX. This study demonstrated that MTX plays a role as a regulator against pentosidine formation and oxidative DNA damage in RA patients.     

The dopamine D1 receptor agonist, but not the D2 receptor agonist, induces gene expression of Homer 1a in rat striatum and nucleus accumbens

Stimulation of dopamine receptors may induce striatal Homer 1a, an immediate-early gene (IEG) that is involved in the molecular mechanism for the signaling pathway of the group I metabotropic glutamate receptors. This study examined the effects of the agonists for dopamine D(1)-like and D(2)-like receptors on gene expression of Homer 1a, in comparison with the IEG c-fos expression, in the discrete brain regions of rats. The D(1)-like agonist SKF38393 (20 mg/kg, s.c.) significantly increased the mRNA levels of Homer 1a in the striatum and nucleus accumbens, but not in the medial prefrontal cortex or hippocampus, 2 h after injection, whereas the D(2)-like agonist quinpirole (1 mg/kg, s.c.) had no significant effect on Homer 1a mRNA levels in any brain region examined. Co-administration of SKF38393 and quinpirole significantly increased Homer 1a mRNA levels in the striatum, nucleus accumbens and hippocampus, while this effect was not significantly greater than that of SKF38393 alone. Any treatment did not affect the mRNA levels of other splicing variants, Homer 1b or 1c. In contrast, combination of both dopamine agonists produced a greater increase than SKF38393 did in the mRNA levels of c-fos in the nucleus accumbens, striatum and substantia nigra. These results suggest that stimulation of D(1)-like receptors, but not D(2)-like receptors, may induce gene expression of Homer 1a in the striatum and nucleus accumbens. However, in contrast to c-fos expression, it is unlikely that co-activation of both D(1)-like and D(2)-like receptors exerts a synergic action on Homer 1a expression in these regions.     

Is central obesity a good predictor of carotid atherosclerosis in Japanese type 2 diabetes with metabolic syndrome?

Metabolic syndrome has been revealed to be a major risk factor for cardiovascular disease (CVD) and early mortality in non-diabetic and diabetic patients. In 2005, the International Diabetes Federation (IDF) and the Examination Committee of Criteria for Diagnosis of Metabolic Syndrome in Japan published new definitions of metabolic syndrome in which central obesity was an indispensable factor. However, the significance of this new definition to CVD in type 2 diabetes has not yet been clarified. A cross-sectional study was conducted with 294 Japanese type 2 diabetic patients without known cardiovascular disease to evaluate the association between metabolic syndrome defined by this new definition and carotid atherosclerosis, and the significance of central obesity for the prediction of the development of carotid atherosclerosis. In a multivariate regression analysis, metabolic syndrome but not central obesity was significantly associated with carotid intima-media thickness (IMT) independent of known cardiovascular risk factors (p<0.05). In addition, whereas carotid IMT was significantly increased according to the increase in the number of components of metabolic syndrome, it was not significantly different between the groups with the same number of components of metabolic syndrome with or without central obesity. These findings suggest that the prediction of the development of carotid atherosclerosis in Japanese type 2 diabetic patients could be improved by the assessment of aggregation of components of metabolic syndrome rather than with or without metabolic syndrome by this new definition.     

Amyloid precursor protein cytoplasmic domain with phospho-Thr668 accumulates in Alzheimer’s disease and its transgenic models: a role to mediate interaction of Aβ and tau

Abnormal accumulation of Aβ and tau in senile plaques (SP) and neurofibrillary tangles (NFTs) is a key event in Alzheimer’s disease (AD). Here, we show that T668-phosphorylated cytoplasmic domain of APP (pT668-ACD) accumulates Aβ and tau in AD and its transgenic models. Anti-pT668 immunostaining of AD brain sections with hydrated autoclave enhancement identified SP neurites and NFTs in which pT668-ACD colocalizes with tau. We produced and examined transgenic (Tg) mice that overexpress human APP695, harboring the double Swedish/London mutation, and develop age-dependently Aβ plaques in the brain. All Aβ plaques contain co-accumulations of pT668-ACD, but co-accumulation of tau appears in only a fraction of Aβ plaques in older animals. We also examined the established tau Tg mice that overexpress the smallest human brain tau isoform and develop neuronal accumulations of tau in older animals. Examination of the old tau Tg mice showed that neuronal cells affected by tau accumulation induce co-accumulation of pT668-ACD. We speculate that in AD brains, extracellular Aβ deposition is accompanied by intracellular accumulation of pT668-ACD, followed by tau accumulation in the SP with dystrophic neurites and that neuronal cells affected by tau accumulation induce co-accumulation of pT668-ACD in NFTs. Thus, pT668-ACD is likely to mediate pathological interaction between Aβ and tau.     

Identification of intracerebral hemorrhage in the early-phase of MM1+2C-type sporadic Creutzfeldt–Jakob disease: A case report

We report a case of early-phase sporadic Creutzfeldt–Jakob disease (sCJD) complicated by intracerebral hemorrhage (ICH), classified as MM1 + 2C-type based on autopsy. A 61-year-old Japanese man presented to our hospital with speaking difficulties including repeated usage of the same words. He was hospitalized on the seventh day after symptom onset, and diffusion-weighted images on magnetic resonance imaging showed hyperintense regions in the frontal cortex and caudate nucleus. On the 11th day after symptom onset, head computed tomography revealed ICH in the right occipital and parietal lobes. Routine laboratory evaluations and angiography revealed no cause of ICH. Myoclonus of the extremities and drowsiness were observed on the 15th day after symptom onset. He reached the state of akinetic mutism approximately two months after symptom onset. The cerebrospinal fluid test revealed positive real-time quaking-induced conversion and 14-3-3 protein. Electroencephalography revealed periodic sharp wave complexes. A clinical diagnosis of probable Creutzfeldt–Jakob disease was made according to the diagnostic criteria. After a relapse of pneumonia, he passed away on the 103rd day after symptom onset. Postmortem examination revealed ICH in the right posterior cingulate gyrus. No pathological change that might have caused ICH was obtained. Although the effect of sCJD on the onset of ICH is undeniable, the cause of ICH was unknown. Prion protein immunohistochemistry revealed the following results: (1) weak synaptic-type deposits in the tissue rarefacted by ICH; (2) synaptic-type deposits in the cerebral cortex, which showed fine vacuoles; and (3) perivacuolar-type deposits in the inferior temporal gyrus and lingual gyrus, which showed frequent large confluent vacuoles. Although it could be considered MM1-type sCJD clinically, this case was neuropathologically diagnosed as having MM1 + 2C-type sCJD. It was shown that ICH may occur in early-phase sCJD. To improve sCJD prognosis, treatment of complications and careful follow up are important. Furthermore, pathological diagnosis is indispensable for sCJD type diagnosis.