Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Intracerebral penetration of carteolol hydrochloride in rats

To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the C_max and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059–0.091 μg/g and 0.321–0.443 μg/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6–0.8 h and 1.3–1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability. Received: 30 October 1996/Final version: 16 December 1996     

Hemodynamic studies of portal hypertension with esophageal varices; a role of left gastric artery and vein

Hemodynamic states of portal hypertension with esophageal varices were studied by scintiphoto splenoportography (SSP) and left gastric angiographies in relation to endoscopic findings. The cases were classified into two groups by SSP. The flow of left gastric vein was hepatofugal in Group I (77.3%), and it was hepatopetal or "to and fro" in Group II (22.7%). Endoscopically, the varices were more severe in Group I than those in Group II. The diameter of left gastric vein was significantly larger in Group I. The values of K.ICG and liver function by blood analysis were also poor in Group I. Moreover, the cases with varices supplied by both left gastric artery and vein showed more severe endoscopic findings and history of hematemesis than those in the cases with varices supplied by left gastric artery alone. In conclusion, the results suggested that the flow of left gastric vein was closely related to the severity of esophageal varices.     

A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths

We found the association of a heterozygous novel MPZ gene point mutation, Ile62Phe in exon 2, with autosomal dominant motor and sensory neuropathy with focally folded myelin sheaths. Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy. Our study suggests that the characteristic pathologic findings of the sural nerve in these patients are closely related to the site and nature of amino acid substitutions of the MPZ gene.     

Axonal damage revealed by accumulation of beta-amyloid precursor protein in HTLV-I-associated myelopathy

We investigated the localization and extent of beta-amyloid precursor protein (APP) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The results from this study show that APP, used as a marker of early axonal damage in HAM/TSP lesions, is more intensively expressed in areas of active-inflammatory lesions than those of inactive-chronic lesions. The close localization to the areas containing inflammation (activation of macrophage/microglia) is striking and suggests that axonal damage is closely associated with inflammation in active-chronic lesions. Although inflammatory cell infiltration in the central nervous system (CNS) is rarely found in inactive-chronic lesions, a few clusters of APP+ axons are found in the spinal cord white matter in some cases. The presence of APP+ axons without relation to inflammatory cells in inactive-chronic lesions, suggest that soluble neurotoxic factors might induce axonal changes in the CNS of HAM/TSP. The occasional myelinated fibers in the anterior and posterior spinal roots in lower thoracic to lumbar levels had APP+ axons, suggesting that spinal nerve roots can be affected in HAM/TSP, especially in lower thoracic to lumbar levels. Impairment of fast axonal transport may contribute to the development of disability in patients with HAM/TSP.     

Warm ischemia and reperfusion injury in diet-induced canine fatty livers

BACKGROUND: Fatty liver is associated with primary nonfunction after liver transplantation, contributing a shortage of suitable liver grafts. Because extensive investigation of mechanisms underlying such nonfunction has been limited largely to rodents, we made a new fatty liver model in dogs and studied primary nonfunction after warm ischemia. METHODS: We developed a diet rich in fat but deficient in choline to induce fatty change in canine liver and investigated effects of 60 min of warm ischemia and reperfusion in dogs with such fatty livers. RESULTS: Microscopically evident steatosis increased with duration of dietary manipulation (up to 12 weeks), as did hepatic total lipid and triglyceride levels. No dog with >30% of steatotic hepatocytes, >445 mg/g hepatic total lipid or >145 mg/g hepatic triglyceride survived after 60 min of warm ischemia. Arterial ketone body ratios decreased and blood endotoxin increased after reperfusion in nonsurvivors. The main histologic finding in livers of nonsurvivors was marked sinusoidal congestion. CONCLUSIONS: Damage to hepatocytes and nonparenchymal cells after warm ischemia and reperfusion was thought to be closely related to sinusoidal microcirculatory disturbances in fatty livers. The canine fatty liver model reported here may be useful in studying the pathology of primary nonfunction and in establishing criteria for allowable degrees of fatty change in potential liver grafts.     

Potential extraperitoneal space continuous with the peri-intestinal space: CT evidence and anatomical evaluation in patients with pneumatosis intestinalis without intestinal ischemia

Purpose  

Extraperitoneal spaces, such as the mesenteric space and the retroperitoneal space, can serve as areas that enable a reduction in the pressure exerted by extraperitoneal fluid collection and infiltrating diseases. In clinical practice, understanding the existence of these decompression spaces (or pathways) is very important for making accurate diagnoses. Here, we evaluated potential anatomical extraperitoneal spaces based on the extraluminal gas distribution in patients with pneumatosis intestinalis without intestinal ischemia.     

Effective exercise intervention period for improving body function or activity in patients with knee osteoarthritis undergoing total knee arthroplasty: a systematic review and meta-analysis

Background

Various systematic reviews and/or meta-analyses examining the effects of pre- or postoperative exercise on body function or activity in patients undergoing total knee arthroplasty (TKA) have been published. However, the interventional period needed to at least improve outcomes is unknown.