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Abstract Aims The accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno‐protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno‐protection. Materials and methods To examine the effects of increased podocyte oligosaccharyltransferase‐48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase‐48kDa subunit abundance in podocytes driven by the podocin promoter. Results Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra‐resolution microscopy of podocytes revealed denudation of foot processes where there was co‐localization of oligosaccharyltransferase‐48kDa subunit and advanced glycation end‐products. Conclusions These studies indicate that increased podocyte expression of oligosaccharyltransferase‐48 kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.

The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program (COPE) on infant cognitive development and maternal coping. A randomized clinical trial was conducted with 42 mothers of low-birth-weight (LBW) premature infants hospitalized in a neonatal intensive care unit (NICU), with follow-up at 3 months' and 6 months' corrected ages. COPE mothers received the four-phase educational-behavioral program that began 2-4 days postbirth and continued through 1 week following discharge from the NICU. Comparison mothers received audiotaped information during the same four time frames. Results indicated that COPE infants had significantly higher mental development scores at a 3 months' corrected age (M = 100.3) than did the comparison infants (M = 93.9), and this difference widened at 6 months' corrected age, with COPE infants scoring 14 points higher. COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants. Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes., (Copyright 2001 John Wiley & Sons, Inc.)

Objective: Mathematical analyses of ventricular fibrillation (VF) have resulted in the derivation of a measure termed the scaling exponent (ScE) that characterizes the duration of VF and probability of defibrillation success. The purpose of this study was to compare the effects of biphasic defibrillation waveform (BDW) and monophasic defibrillation waveform (MDW) rescue shocks on ScE in a swine model of prolonged VF., Methods: Utstein guidelines for the laboratory study of cardiopulmonary resuscitation were followed. Twenty mixed-breed domestic swine (mass range 20.5-26.8 kg) were instrumented and randomized to receive either MDW or BDW rescue shocks. Ventricular fibrillation was induced and untreated for a nonintervention interval of 8 minutes. Rescue shocks were delivered at 8, 10, and 12 minutes of elapsed VF time. The energy sequence for the three MDW shocks was 70, 100, and 150 J (approximately 3, 4, and 6 J/kg). All BDW shocks were delivered at 50 J (approximately 2.5 J/kg). Only VF was shocked. Chest compressions and drugs were not provided. Rhythm analysis and ScE calculation were performed offline. Continuous and discontinuous linear regression models were fit to plots of ScE vs time. Defibrillation success and progression of ScE slope were analyzed using Fisher's exact test, paired t-tests, and repeated-measures analysis of variance (ANOVA)., Results: Baseline characteristics were similar for both groups. Successful termination of VF occurred on the first rescue shock in 1 of 10 (10%) in the MDW group and 3 of 10 (30%) in the BDW group; this difference was not statistically significant (p = 0.58). No other defibrillation successes were observed. No animals achieved return of spontaneous circulation. The ScE values during the protocol progressed from 1.330 (95% CI = 1.287 to 1.373) to 1.724 (95% CI = 1.603 to 1.845) for MDW and 1.338 (95% CI = 1.261 to 1.415) to 1.639 (95% CI = 1.530 to 1.745) for BDW. Both groups showed a trend toward increasing ScE values with successive rescue shocks. Repeated-measures ANOVA using both continuous and discontinuous models demonstrated no difference in overall ScE slope progression between study groups., Conclusions: Mode of defibrillation waveform (BDW vs MDW) does not appear to impact ScE trends. Additional studies must be performed to better evaluate the clinical implications of this finding.

The large family of CD44 splice variants are likely to serve multiple functions in the embryo and in the adult organism. This is reflected in their complex patterns of expression. In molecular terms these functions are largely unknown. Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis. Metastasis-promoting splice variants differ from those that seem not to have a role in the induction of metastasis by the formation of homomultimeric complexes in the plasma membrane of cells. This may increase their affinity to ligands such as hyaluronate. The affinity can be further regulated over a range from low to very high by cell-specific modification. The fact that CD44v epitopes are found on normal epithelial cells such as skin, cervical epithelium and bladder enforces cautious evaluation of the significance of CD44v expression in human cancer. Nevertheless, certain epitopes can serve as tools in early diagnosis of certain cancers and will facilitate the development of specific targeted therapy.

The diuretic and clinical efficacy and safety of piretanide, a new high-ceiling loop diuretic, was determined in patients with mild to moderately severe congestive heart failure. Piretanide (n = 20) administered orally in a daily dosage of up to 24 mg was compared with placebo (n = 18) for 28 days, using a double-blind, randomized, parallel design. Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24-hour fractionated urine collections were obtained. Piretanide caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours. While occasional kaliuretic response was noted, it did not significantly increase 24-hour urinary potassium excretion. Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia. An improvement in New York Heart Association functional class status was noted after piretanide therapy. In contrast, patients who received placebo exhibited no significant improvement. BUN increased in nine piretanide-treated patients; two were discontinued from the study because of progressive azotemia. However, there was no significant increase in serum creatinine levels. Other blood, physical, ECG, and audiometric examinations also revealed no significant abnormalities. The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium-sparing properties.