Vascular-Resident CD169-Positive Monocytes and Macrophages Control Neutrophil Accumulation in the Kidney with Ischemia-Reperfusion Injury

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169⁺ monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169⁺ cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169⁺ monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169⁺ cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C^lo monocytes into CD169⁺ cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C^lo subset of CD169⁺ monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169⁺ monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.     

QT dispersion correlates with systolic rather than diastolic parameters in patients receiving anthracycline treatment

OBJECTIVE: The aim of this study was to investigate the relation of QT dispersion to left ventricular (LV) systolic and diastolic function in patients undergoing anthracycline therapy. METHODS: We used echocardiography to evaluate LV systolic and diastolic function and electrocardiography to evaluate QT dispersion and corrected QT dispersion (QTcD) in patients with hematological diseases, who received anthracycline therapy. PATIENTS: Seventy-two patients with hematological diseases who were receiving anthracycline treatment were enrolled in the present study. RESULTS: LV end-diastolic diameter or LV end-systolic diameter had a significant positive correlation to QTcD (r = 0.35, p < 0.01, r = 0.43, p < 0.01). Also left ventricular ejection fraction of (LVEF) or fractional shortening had a significant negative correlation to QTcD (r = -0.46, p < 0.001, r = -0.27, p = 0.02). The highest QTcD group had a significantly larger LV end-diastolic diameter or LV end-systolic diameter than the lowest QTcD [48.5 +/- 5.7 vs. 44.4 +/- 4.5 (mm), p < 0.001, 34.1 +/- 6.4 vs. 28.8 +/- 4.3 (mm), p < 0.001] and the highest QTcD group had a significantly lower LVEF than the lowest QTcD [57.5 +/- 8.0 vs. 65.5 +/- 6.4 (%), p < 0.001]. On the other hand, none of the diastolic function markers were significantly correlated with QTcD. CONCLUSION: We concluded that increased QTcD is correlated with LV dilation and systolic dysfunction induced by anthracycline therapy, and does not reflect a dispersion of ventricular repolarization or asynchronous motion.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

An XXX female with essential thrombocythemia

We describe an XXX female patient accompanied with essential thrombocythemia. To our knowledge this is the first case ever to have been reported. The patient was asymptomatic, but her platelet count had increased to 111.2 x 10(4)/microliter, and she was diagnosed as having essential thrombocythemia based on the diagnostic criteria of the Polycythemia Vera Study Group. At the same time, chromosome analysis of bone marrow cells revealed that she was an XXX female. The patient remained asymptomatic throughout the course of treatment.     

Characteristics of earlier atherosclerotic involvement in adolescent patients with Kawasaki disease and coronary artery lesions: significance of gray scale median on B-mode ultrasound

ObjectiveTo test the hypothesis that textural changes in the carotid intima–media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs).MethodsEighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima–media thickness (CIMT), elastic property (E_p), and first- and second-order statistics.ResultsKD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH.ConclusionHigher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.