Natural regulatory T cells control coronary arteriolar endothelial dysfunction in hypertensive mice

Coronary artery disease in patients with hypertension is increasing worldwide and leads to severe cardiovascular complications. The cellular and molecular mechanisms that underlie this pathologic condition are not well understood. Experimental and clinical research indicates that immune cells and inflammation play a central role in the pathogenesis of cardiovascular diseases. Recently, it has been reported that CD4(+)CD25(+) regulatory T cells (Tregs) regulate heart fibrosis in hypertension. In this study, we determined the role of Tregs in coronary arteriolar endothelial dysfunction in angiotensin II-dependent hypertensive mice. Mice infused with angiotensin II had significantly increased blood pressure, as determined using telemetry, and apoptotic Treg numbers, as measured using flow cytometry. The mice displayed inflammation, assessed by macrophage activation/infiltration into coronary arterioles and the heart, and increased local tumor necrosis factor-α release, which participates in reduced coronary arteriolar endothelial-dependent relaxation in response to acetylcholine using an arteriograph. Hypertensive mice injected with Tregs isolated from control mice had significantly reduced macrophage activation and infiltration, reduced tumor necrosis factor-α release, and improved coronary arteriolar endothelium-dependent relaxation. Our novel data indicate that Tregs are important in the development of coronary arteriolar endothelial dysfunction in hypertension. These results suggest a new direction in the investigation of vascular disease in hypertension and could lead to a therapeutic strategy that involves immune system modulation using Tregs.     

Absorption enhancement studies of clopidogrel hydrogen sulphate in rat everted gut sacs

Objectives Clopidogrel, a thienopyridine antiplatelet agent, is a poor aqueous soluble compound and a P‐glycoprotein (P‐gp) efflux pump substrate. These two factors are responsible for its incomplete intestinal absorption. In this study, we have attempted to enhance the absorption of clopidogrel by improving its solubility and by inhibiting intestinal P‐gp activity. Methods Solubility enhancement was achieved by preparing solid dispersions. Quinidine and naringin were selected as P‐gp inhibitors, whilst tartaric acid was selected as the intestinal absorption enhancer. Absorption studies were performed using the everted gut sac model prepared from rat jejunum. The determination of clopidogrel was performed by high performance liquid chromatography. Key findings We noticed an enhancement of clopidogrel absorption by improving its solubility or by inhibiting the P‐gp activity. The greatest results were obtained for solid dispersions in the presence of P‐gp inhibitors at their highest concentrations, with an absorption improvement of 3.41‐ and 3.91‐fold for naringin (15 mg/kg) and quinidine (200 µm ), respectively. However, no clopidogrel absorption enhancement occurred in the presence of tartaric acid. Conclusions Naringin, a natural compound which has no undesirable side effects as compared with quinidine, could be used as a pharmaceutical excipient in the presence of clopidogrel solid dispersions to increase clopidogrel intestinal absorption and therefore its oral bioavailability.     

Citrulline: From metabolism to therapeutic use

Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of citrulline may be used to deliver available nitrogen for protein homeostasis in peripheral tissues and as an arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that citrulline is efficiently transported across the intestinal luminal membrane by a set of transporters belonging to the B^0,+, L, and b^0,+ systems. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations, because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Hence, citrulline could play a pivotal role in maintaining protein homeostasis and is a promising pharmaconutrient in nutritional support strategies for malnourished patients, especially in aging and sarcopenia.     

Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation recipients: clinical characteristics of infections and vaccine-breakthrough infections, 1989-2005

Streptococcus pneumoniae infections can cause serious systemic disease in patients following hematopoietic stem cell transplantation (HSCT), and the response to pneumococcal vaccine is inadequate in most HSCT recipients. We evaluated the clinical spectrum of pneumococcal disease and vaccine-breakthrough infections in HSCT recipients at our cancer center in a retrospective analysis of all consecutive episodes of S. pneumoniae infection from 1989 through 2005. During the study period, 7888 patients underwent HSCT at our center; we identified 47 HSCT recipients with 54 S. pneumoniae infections. The overall incidence of S. pneumoniae infection was 7 per 1000 HSCTs. The incidence was higher in recipients of allogeneic grafts than in recipients of autologous grafts (9 vs. 5 per 1000 HSCTs, respectively; p 相似文献   

Posterior-reversible encephalopathy in hemodialysis

Posterior-reversible encephalopathy syndrome (PRES) is a recently clinicoradiologic entity caused by numerous medical conditions and characterized by acute-neurologic disorders, such as headaches, confusion, seizures associated with arterial hypertension. MRI characteristics are typical. The rapid diagnosis is of capital importance due to a potential reversibility.