F(2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes

BACKGROUND: The recently discovered arachidonic acid derivatives, isoprostanes, are increased in pathological conditions associated with oxidative stress, such as diabetes. No role has yet been described for isoprostanes during the development of diabetic nephropathy. Cell culture in high ambient glucose has been used as a model in elucidating cellular mechanisms underlying diabetic nephropathy. Among the growth factors involved in the effect of high glucose, transforming growth factor-beta (TGF-beta) has been described as playing a key role in the development of nephropathy. METHODS: Streptozotocin-induced diabetic rats were supplemented in their diet with the antioxidant vitamin E (1000 U/kg diet). Blood and urine samples were taken to determine renal function and isoprostane concentration, as determined by gas chromatography/mass spectrometry. Glomerular mesangial and endothelial cells were cultured in high ambient glucose to determine the synthesis of isoprostanes and the role of isoprostanes in high glucose-induced synthesis of TGF-beta. RESULTS: Streptozotocin-induced diabetic rats had marked increases in plasma levels and urinary excretion rates of F(2)-isoprostanes. Dietary supplementation with vitamin E normalized (plasma) and reduced (urine) isoprostane levels and, surprisingly, improved proteinuria and blood urea nitrogen (BUN) levels. High ambient glucose increased F(2)-isoprostane synthesis in glomerular endothelial and mesangial cells in culture. Incubation of glomerular cells with F(2)-isoprostanes stimulated the production of TGF-beta. CONCLUSIONS: Increased F(2)-isoprostane synthesis during diabetes appears to be responsible in part for the increase in renal TGF-beta, a well-known mediator of diabetic nephropathy.     

IMRT for breast. a planning study.

BACKGROUND AND PURPOSE: To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. PATIENTS AND METHODS: A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.     

Anxiety and Epilepsy: What Neurologists and Epileptologists Should Know

Although there has been increasing recognition of psychiatric comorbidity in epilepsy, most research and attention in this area has focused on depression. However, comorbid anxiety in epilepsy is highly prevalent, affecting more than 40 % of patients in some reports. Many important outcomes are significantly impacted by anxiety in epilepsy, including quality of life, mortality, and seizure status. Recent evidence from epidemiologic studies suggests a bidirectional association of anxiety and epilepsy, and there is mounting evidence for possible common pathophysiology underlying anxiety and epilepsy. Despite this importance, anxiety is under-recognized and undertreated in clinical practice. A variety of anxiety symptoms are seen in epilepsy, including symptoms exclusively before, during or after seizures (peri-ictal anxiety), symptoms resembling primary anxiety disorders, and anxiety directly related to epilepsy or its treatment. Key therapeutic approaches include pharmacotherapy or cognitive behavioral therapy for most forms of interictal anxiety and better seizure control for peri-ictal anxiety.     

Early heparinization decreases the incidence of left atrial thrombi detected by intracardiac echocardiography during radiofrequency ablation for atrial fibrillation

INTRODUCTION: We reviewed our experience in managing intracardiac ultrasound-detected left atrial thrombus and analyzed the impact of the timing of heparin therapy on thrombus incidence. METHODS AND RESULTS: We identified 508 patients undergoing ablation procedures for atrial fibrillation in which intracardiac ultrasound was used. All patients received unfractionated heparin during the procedure: 31 patients before the first transseptal puncture (preTS1), 257 between the first and second transseptal punctures (TS1-TS2), and 220 following both punctures (postTS2). By using intracardiac echocardiography (ICE), thrombus was detected in 30 of these 508 patients (5.9%). Of these, 29 were in the left atrium and constituted our study group. In 21 patients, the thrombi were successfully aspirated from the left atrium using strong suction through the transseptal sheath. All patients in whom thrombi were aspirated did well without neurological event or death. When patients received heparin therapy either preTS1 or TS1-TS2, there was a significant decrease in the occurrence of ICE-detected left atrial thrombus compared with those who received heparin postTS2 (0 of 31 patients (0%) preTS, 9 of 257 (3.5%) TS1-TS2, and 20 of 220 (9.1%) postTS2; (preTS1 vs postTS2, p = 0.01; preTS2 [preTS1 and TS1-TS2] vs postTS2, p < 0.001). CONCLUSION: Early administration of intravenous heparin, specifically before transseptal puncture, decreases the incidence of left atrial thrombi.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.