Pharmacokinetics of denopamine in hemodialysis patients.

The pharmacokinetics of denopamine on a hemodialysis day and on an interdialysis day was evaluated in 11 hemodialysis patients. Tmax was the only pharmacokinetical parameter that differed significantly between healthy volunteers and hemodialysis patients. It is suggested that denopamine can be administered to hemodialysis both on hemodialysis days and on interdialysis days without dosage adjustments.     

Neuromedin B and gastrin-releasing peptide mRNAs are differentially distributed in the rat nervous system

The bombesin-like peptides are a family of structurally related amidated peptide ligands that are known to have a variety of potent pharmacological actions on various cells, including neurons in the rat brain. Two mammalian representatives of the bombesin family of peptides have been identified, gastrin-releasing peptide (GRP) and neuromedin B (NMB). Previously, we cloned the rat preproGRP gene and determined the locations of neurons expressing this gene using in situ hybridization. In this study, we describe the structure and sequence of the rat preproNMB gene, and the first detailed cellular localization of preproNMB mRNA in rat brain using in situ hybridization. Nucleotide sequence analysis of cDNA and genomic clones reveals a 117 amino acid precursor whose overall structure is similar to that described for human preproNMB. Sequence similarity between the rat NMB and GRP genes is observed only over a limited 10 amino acid sequence encoding the carboxy termini of the GRP and NMB peptides, the region shown to be necessary and sufficient for high-affinity receptor binding. In situ hybridization studies performed with cRNA probes specific for NMB or GRP mRNA show that the distribution of cells expressing either mRNA in brain is very distinct. NMB mRNA is found most prominently in the olfactory bulb, dentate gyrus, and dorsal root ganglion. In contrast, the highest levels of GRP mRNA are observed in the forebrain (isocortex and hippocampal formation). This heterogeneity of mRNA distribution for these peptides suggests that these 2 structurally related peptides may have very distinct functions as neuropeptides in the rat nervous system.     

Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary beta-amyloid deposition: a case report]

We report a sporadic case of unusual cerebral amyloid angiopathy (CAA) with prominent capillary involvement. A 67-year-old doctor developed gait disturbance, resting tremor and rigidity. He was diagnosed to have Parkinson's disease, for which the treatment with levodopa was effective. Four years later he began to exhibit progressive cognitive decline and behavioral abnormalities consisting of hallucination and agitation. Subsequently, his condition steadily worsened and became bedridden with severe dementia, and he died eight years after the disease onset. During the clinical course, there had been no episode of stroke. Postmortem examinations revealed the typical pathology of Parkinson's disease with frequent cortical Lewy bodies in the amygdala. The most striking pathological feature of this patient was widespread CAA where prominent beta-amyloid (A beta) deposition was observed in the capillaries of the neocortex, most pronouncedly in the occipital lobe, as well as leptomeningeal and cerebral medium-sized and small vessels. Further, perivascular plaques were found in half of the amyloid-laden capillaries. Tau-positive dystrophic neurites were only sparsely detectable within a few perivascular plaques. Despite the severe A beta pathology, there was no microaneurysmal dilatation, fibrinoid necrosis or vascular occlusion. There was only one small ischemic lesion in the brain. The cerebral white matter was unremarkable. Senile plaques of neuritic type and neurofibrillary tangles were mostly limited to the hippocampal regions and, to a lesser degree, in the amygdaloid nucleus, which did not meet the neuropathological criteria of Alzheimer's disease. On the gene analyses, his apolipoprotein E (ApoE) genotyping was verified to be heterozygous epsilon 3/epsilon 4, and no mutation was seen in exons 16 and 17 of the amyloid precursor protein gene. Severe A beta capillary angiopathy as seen in our patient is exceptional in sporadic CAA. Further, A beta angiopathy of this patient was notable in the absence of an associated cerebrovascular disease despite prominent A beta deposition in the vessel walls. Regarding the development of his severe dementia, the limbic pathology of Lewy body disease might be one of the potential causes, but A beta angiopathy appears more likely because of its severity. We speculate that widespread A beta deposition disregulates the blood-brain barrier of the capillaries leading to a disturbance of the microcirculation throughout the cerebral cortex without obvious ischemic disintegration of the neuropil. We should take into consideration that A beta angiopathy can present as progressive dementia without cerebrovascular disease.     

Identification of benzoylcarnitine in the urine of a patient of hyperammonemia

Benzoylcarnitine was identified in the urine of a patient with a carbamoyl-phosphate synthase I deficiency for whom sodium benzoate and L-carnitine had been used to treat hyperammonemia. This is a newly identified metabolite of benzoate. Its excretion in the urine was increased day by day at the administration of both sodium benzoate and L-carnitine from 0.10 to 2.25 mmol/g creatinine. Since there is the possibility of a secondary carnitine deficiency and an increase of benzoyl toxicity after long-term therapy with benzoate supplementation and protein restriction, it is important to monitor the urinary excretion of benzoylcarnitine.     

Serum levels of KL-6 reflect disease activity of interstitial pneumonia associated with ANCA-related vasculitis.

OBJECTIVE: KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. METHODS: Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. PATIENTS: We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. RESULTS: Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA-positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. CONCLUSION: These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.