Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice

Despite the physiologic importance of vitamin E, in particular its alpha-tocopherol (alpha-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for alpha-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of alpha-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma alpha-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated alpha-T content of their abnormally large plasma HDL-like particles. This increase in plasma alpha-T in SR-BI knockout mice was accompanied by a significant decrease (65-80%) in the alpha-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the alpha-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring alpha-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of alpha-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein alpha-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.     

Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.     

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before ( t ₀) and immediately after ( t ₁) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t ₀ and t ₁, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.     

Prevalence of Infections After In-Office Hysteroscopy in Premenopausal and Postmenopausal Women

Study Objective

To estimate the incidence of infection after diagnostic and operative hysteroscopic procedures performed in an in-office setting with different distension media (saline solution or CO₂).

The immunological effects of extracorporeal photopheresis unraveled: induction of tolerogenic dendritic cells in vitro and regulatory T cells in vivo

Extracorporeal photopheresis (ECP) may represent an alternative to immunosuppression, as a means of reducing rejection after thoracic organ transplantation. The mechanism by which ECP exerts its protective effects has, until now, remained elusive. We analyzed peripheral blood mononuclear cells of four children with chronic heart and lung transplant rejection, who received ECP in addition to conventional immunosuppressive treatment. The effects of ECP were evaluated at each cycle, comparing blood samples from the same patient collected before and after treatment. In vitro, peripheral blood mononuclear cells treated with ECP undergo apoptosis and are phagocytosed by immature dendritic cells, which, in turn, acquire a tolerogenic phenotype. The frequency of T cells, with a regulatory phenotype and strong suppressive activity, was significantly increased in the blood of ECP-treated patients. The immunomodulatory effects of ECP may be explained by its ability to increase the frequency of regulatory T cells with inhibitory action on transplant immune rejection.     

Surgical and radiological management of uterine fibroids--a UK survey of current consultant practice

BACKGROUND: The aim of this study was to determine the current surgical and radiological management of uterine fibroids by consultants working in the UK. METHODS: A structured questionnaire was posted to all 1439 UK consultants. Non-responders were sent one reminder. The main outcome measures were surgical route and technique used for myomectomy, and the use and availability of uterine artery embolization (UAE). RESULTS: Eight hundred fifty-two (59%) consultants replied. Seven hundred thirty-five (86%) admitted to regular sessions of gynecologic surgery, and 75% of this group performed open myomectomy, 16% laparoscopic myomectomy, and 66% hysteroscopic myomectomy. Open myomectomy: Forty-one percent of consultants performed open surgery on uteri equivalent to 12-week gestational age or less, 87% prescribed preoperative gonadotrophin-releasing hormone agonists (GnRHa) in order to reduce surgical bleeding, with 35% using myomectomy clamps, 23% tourniquets, and 19% vasoconstrictors. Laparoscopic myomectomy: The largest uterine size the majority would attempt was equivalent to a 12-week gestation, 58.6% used preoperative GnRHa, 21% used intraoperative vasoconstrictors, and 1.4% tourniquets in order to minimize bleeding. Hysteroscopic myomectomy: As with laparoscopic myomectomy, the largest uterine size the majority would attempt was equivalent to a 12-week pregnancy. Blood transfusion: Twenty per cent, 10%, and 7% reported the need for blood transfusion in up to 10% of patients undergoing open, laparoscopic, or hysteroscopic myomectomy, respectively. UAE: Fifty-one percent have access to UAE and 40% have referred at least one patient in 2001. CONCLUSIONS: Open and hysteroscopic myomectomy are frequently utilized in contrast to laparoscopic myomectomy. The reported rate of blood transfusion appears low. Although UAE is widely available, the majority of patients are still managed surgically.     

Abnormal pH-sensing of platelet Na+/H+ exchanger in patients with cardiac syndrome X

An enhanced activity of Na⁺/Li⁺ countertransport, studied as a surrogate of Na⁺/H⁺ exchanger, has been described in red blood cells of patients with cardiac syndrome X. In this study we investigated whether abnormalities in the activity of platelet Na⁺/H⁺ exchanger (NHE) also existed in syndrome X patients and whether such abnormality was associated with platelet activation. Platelet NHE activity was evaluated in 21 syndrome X patients and 18 controls by measuring the pH recovery in platelets after acid loading and/or thrombin stimulation. The linear correlation existing between the initial intracytoplasmic pH (pH_i) values and the maximal velocity of pH recovery allowed to calculate the values of slope and intercept at pH_i=6.6 (I_pH6.6) for each individual. Urinary excretion of the major TXB₂ metabolite, 11-dehydro-TXB₂ was measured in 15 syndrome X patients and 15 controls. The acidification-induced NHE activity resulted significantly higher in syndrome X patients compared to controls. Indeed, slope values were 0.75±0.29 and 0.5±0.23 min⁻¹ in patients and controls, respectively (P=0.01), while I_pH6.6 values were 0.24±0.1 and 0.17±0.1 ΔpH/min (P=0.04). The thrombin-stimulated NHE activity, however, was not different in the two groups and no significant difference in the urinary excretion of 11-dehydro-TXB₂ between patients and controls (median 920 vs. 765 pg/mg creatinine, respectively) (P=0.32) was also found. Thus our data demonstrate an alkaline shift in pH-dependence of platelet NHE of syndrome X patients. This abnormality does not seem to be associated with increased platelet activation.