P-glycoprotein and MRP1 expression and reduced ritonavir and saquinavir accumulation in HIV-infected individuals

OBJECTIVES: Efflux transporters may play a role in lowering intracellular drug concentrations. As the HIV protease inhibitors are substrates for the efflux transporters P-glycoprotein and MRP, we wished to investigate whether differences in expression of these transporters on human lymphocytes correlated with intracellular concentrations of ritonavir and saquinavir. PATIENTS AND METHODS: Drug efflux transporter expression (P-glycoprotein and MRP1) on peripheral blood mononuclear cells isolated from HIV-positive patients was investigated using flow cytometry. In addition, plasma and intracellular ritonavir and saquinavir concentrations were measured by HPLC/mass spectrometry. The ratio of intracellular:plasma drug concentration was used to quantify intracellular drug accumulation. RESULTS: Patients with lower MRP1 expression (相似文献   

A novel subset of putative stem/progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung

Identification of the nature of severe acute respiratory syndrome (SARS)-infected cells is crucial toward understanding the pathogenesis. Using multicolor colocalization techniques, we previously reported that SARS⁺ cells in the lung of fatally infected patients expressed the only known functional receptor, angiotensin-converting enzyme 2, and also a binding receptor, liver/lymph node–specific ICAM-3–grabbing non-integrin (CD209L). In this study, we show that SARS-infected cells also express the stem/progenitor cell markers CD34 and Oct-4, and do not express cytokeratin or surfactant. These putative lung stem/progenitor cells can also be identified in some non-SARS individuals and can be infected by SARS-coronavirus ex vivo. Infection of these cells may contribute to the loss of lung repair capacity that leads to respiratory failure as clinically observed.     

Use of intramuscular botulinum toxin in Malaysian children with cerebral palsy

A study was carried out to determine the clinical effectiveness of intramuscular botulinum toxin type A (BTX) in the treatment of spasticity or dystonia in 58 consecutive children with cerebral palsy (CP). The effectiveness of the treatment was determined by the reduction of spasticity and global parental perception scale. The mean age of treatment was six years and the most frequent aim of treatment (91.1%) was functional improvement. The median reduction of spasticity as measured by modified Ashworth scale was 1. The short term outcome was graded as excellent or good by 44.6% and satisfactory by 38.4% of parents. Patients with dyskinetic Cerebral Palsy had the best response. Adverse effects were minimal. BTX treatment is modestly effective in the majority of our patients with spastic and dyskinetic cerebral palsy.     

Peripheral arterial disease in general and diabetic population

Peripheral arterial disease (PAD) is stenosis or occlusion of peripheral arterial vessels by atherosclerotic plaque. It may present as intermittent claudication, rest pain and impotence. PAD of the lower limbs is the third most important site of atherosclerotic disease after coronary heart disease and cerebrovascular disease. Increasing age, family history, smoking, hypertension, dyslipidemia and more decisively diabetes are significant risk factors. PAD is a clinical condition that has often been neglected, underdiagnosed, undertreated and has a serious outcome. It may lead to nonhealing wounds, gangrene and amputation of the lower limbs. Hence, early identification of patients at risk of PAD and timely referral to the vascular surgeon in severe cases is crucial.     

Nasopharyngeal carcinoma among the Bidayuh of Sarawak,Malaysia: History and risk factors

Nasopharyngeal carcinoma (NPC) is a cancer of the epithelial cells lining the nasopharynx. The incidence of NPC has a distinct geographical distribution, mainly affecting the Chinese population of Southern China. In Malaysia, this cancer is exceptionally prevalent among males. There is a high incidence rate of NPC among the Bidayuh natives in Sarawak, Malaysia. Other than epidemiology reports, there has not been an article describing plausible cancer risk factors contributing to NPC within this native group. Researchers are still trying to understand the reasons the Bidayuh and Southern Chinese are highly susceptible to NPC. This article discusses the risk factors of developing NPC: Epstein-Barr virus infection, genetic predisposition, diet, environmental exposure and tobacco smoking. There is a need to improve the understanding of the role of risk factors to identify new ways to prevent cancer, especially among high-risk groups.     

Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment

Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment.     

Combined Low Dose Rate Brachytherapy and External Beam Radiation Therapy for Intermediate-Risk Prostate Cancer

Introduction

This is a retrospective study conducted to report the tumor control and late toxicity outcomes of patients with intermediate-risk prostate cancer undergoing combination external beam radiation therapy and low dose rate brachytherapy (LDR-PB).