The NUGGET study: NIR ultra gold-gilded equivalency trial.

This study should clarify whether the gold-coated NIROYAL stent is equivalent to the stainless steel NIR stent. Patients were randomized to either NIR stent (n = 298) or a NIROYAL stent (n = 305). The primary endpoint was the minimum lumen diameter of the target lesion at 6 months postprocedure. Secondary endpoints focused on clinical events. At 30 days, adverse events were similar in both groups. At 6 months, the minimal lumen diameter was 1.83/1.64 mm (P < 0.001; 95% CI = 0.08-0.30) and the angiographic restenosis rate was 20.6%/37.7% (P < 0.001; 95% CI = -24.7 to -9.3) for NIR/NIROYAL. The 6-month MACE rates were NIR 7.4% and NIROYAL 10.5% (95% CI = -7.7 to 1.4). Compared to stainless steel stent, the NIROYAL stent demonstrated a smaller minimal lumen diameter, a higher late loss (i.e., higher neointimal hyperplasia in spite of a significantly better initial gain), with higher restenosis and similar MACE rates at 6 months.     

Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2

Recent findings have challenged the current view of Plasmodium falciparum (P falciparum) blood-stage biology by demonstrating the cytoadhesion of early ring-stage-infected erythrocytes (rIEs) to host endothelial cells and placental syncytiotrophoblasts. The adhesion of rIEs was observed only in parasites that bind to the placenta via chondroitin sulfate A (CSA). In this work, a panel of mouse monoclonal antibodies (mAbs) that specifically inhibit cytoadhesion of rIEs but not of mature IEs was generated The previously described ring surface protein 2 (RSP-2), a 42-kDa protein, was identified as the target of the ring-stage-specific mAbs. Time course surface fluorescence experiments revealed a short overlap (approximately 4 hours) of expression between RSP-2 and P falciparum erythrocyte membrane protein 1 (PfEMP1). Their consecutive expression enables IEs to adhere to endothelial cells during the entire blood-stage cycle. During this study, a new phenotype was detected in parasite cultures, the adhesion of normal erythrocytes (nEs) to endothelial cells. All adherent nEs were coated with RSP-2. Immunolocalization studies show that RSP-2 is a rhoptry-derived protein that is discharged onto the erythrocyte membrane during contact with merozoites. Our results identify RSP-2 as a key molecule in sequestration of young blood-stage forms and nEs to endothelial cells.     

Abdominal obesity is associated with potassium depletion and changes in glucose homeostasis during diuretic therapy

The activation of the renin-angiotensin system (RAS) is an important mechanism that contributes to hypertension in obese individuals. Thiazide diuretics also activate the RAS in response to volume contraction and can lead to a decrease in serum potassium values and glucose metabolism abnormalities. To evaluate the impact of abdominal obesity on potassium depletion and glucose homeostasis in hypertensive patients receiving thiazide therapy, the authors studied 329 hypertensive patients without known diabetes or impaired renal function. Patients were stratified into 2 major groups according to whether they used thiazide diuretic therapy, and each group was further divided in 2 subgroups according to the presence of abdominal obesity. The authors demonstrated that obese patients receiving diuretic therapy had lower plasma potassium levels and higher glucose values compared with nonobese patients receiving diuretic therapy. In conclusion, abdominal obesity predisposes to potassium depletion during diuretic therapy in association with effects on glucose homeostasis.     

Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis： Involvement of cyclooxygenases and heat shock protein 70

AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process, METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-lp. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.     

Factors associated with preservation of C-peptide levels at the diagnosis of type 1 diabetes

Aims

The level of C-peptide can identify individuals most likely to respond to immune interventions carried out to prevent pancreatic β-cell damage.The aim of the study was to evaluate factors associated with C-peptide levels at type 1 diabetes (T1D) diagnosis.

Blood activity of Cu/Zn superoxide dismutase, glutathione peroxidase and catalase in Alzheimer's disease: a case-control study

Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPx) and catalase, which are the three main enzymes involved in cellular protection against damage due to oxygen-derived free radicals have been assayed in plasma and erythrocytes obtained from subjects with dementia of the Alzheimer type (DAT) and from controls. Blood samples were obtained from 25 patients with DAT and from age-matched subjects without diagnoses of neurological disease (non-DAT), as well as from younger individuals (reference group). Using appropriate statistical procedures, the three enzyme activities measured in blood of the elderly were decreased if compared to the younger reference group. Moreover, a significant increase in erythrocyte Cu/Zn SOD and catalase activities of DAT patients was observed compared to the non-DAT group. These results are discussed taking the free radical theory of aging into consideration.     

Comparison of N-glycan pattern of recombinant human coagulation factors II and IX expressed in Chinese hamster ovary (CHO) and African green monkey (Vero) cells

The N-glycan patterns of recombinant human coagulation factors II (rF-II) and IX (rF-IX), derived from both transfected Chinese hamster ovary (CHO) cells and African green monkay (Vero) cells produced at industrial scale, were analyzed by binding to carbohydrate-specific lectins and were compared with the glycan structure of human plasma-derived coagulation factors. Human plasma-derived coagulation factors II (hpF-II) and IX (hpF-IX) exhibited complex-type glycan structures with carbohydrate chains capped with (2–6)-sialic acid. Terminal galactose-(1–4)-N-acetylglucosamine units were detected in hpF-IX. Both CHO cell-derived rF-II and rF-IX exhibited complex-type glycosylation and contained (2–3)-sialic acid in addition to terminal galactose-(1–4)-N-acetylglucosamine. Vero cell-derived rF-IX exhibited a complex-type glycan structure similar to that of CHO cell-derived rF-IX. In contrast, rF-II produced by Vero cells exhibited a glycan microheterogeneity composed of hybrid-type glycosylation containing high-mannose structures and complex-type glycosylation containing (2–3)-sialic acid. Galactose-(1–4)-N-acetylglucosamine structures and a low concentration of (2–6)-sialic acid were detected in both microheterogeneity fractions of Vero cell-derived rF-II. Although different in their carbohydrate structures, coagulation factors II and IX obtained recombinantly from both transformed CHO cells and Vero cells exhibited coagulation activities comparable with the plasma-derived proteins.     

A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes doselimiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. intwo equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.