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This article presents the struggle between social justice and market justice within the current health care system, specifically issues affecting neonatal care. Community benefit is described and discussed as an aspect of social justice demonstrated by hospitals. The federal and state Children's Health Insurance Program also is discussed in relation to social justice and health care costs. Implications for managers and executives overseeing neonatal care are presented in relation to the economic and social issues.

This study investigates proteomic analysis of urinary samples as a non-invasive method to detect acute rejection of renal allografts. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to analyze urinary samples in 19 patients with different grades of subclinical or clinical acute rejection (BANFF Ia to IIb), 10 patients with urinary tract infection and 29 patients without evidence of rejection or infection. A distinct urinary polypeptide pattern identified 16 out of 17 cases of acute tubolointerstitial rejection, but was absent in two cases of vascular rejection. Urinary tract infection resulted in a different polypeptide pattern that allowed to differentiate between infection and acute rejection in all cases. Potentially confounding variables such as acute tubular lesions, tubular atrophy, tubulointerstitial fibrosis, calcineurin inhibitor toxicity, proteinuria, hematuria, allograft function and different immunosuppressive regimens did not interfere with test results. Blinded analysis of samples with and without rejection showed correct diagnosis by CE-MS in the majority of cases. Detection of acute rejection by CE-MS offers a promising non-invasive tool for the surveillance of renal allograft recipients. Further investigation is needed to establish polypeptide patterns in vascular rejection and to explore whether changes in the urinary proteome occur before the onset of histologically discernible rejection.

Background: New insights into the pathogenesis and treatment of diabetic renal disease may emerge from recent advances in proteomics using high-throughput mass spectrometry (MS) of urine., Methods: Using a combination of online capillary electrophoresis (CE) and MS we evaluated urinary polypeptide patterns in four groups of type 2 diabetic patients matched for age, gender, and diabetes duration, including 20 normoalbuminuric patients with and 20 without diabetic retinopathy, 20 microalbuminuric patients with diabetic retinopathy, and 18 macroalbuminuric patients with diabetic retinopathy. Furthermore, changes in urinary polypeptide patterns during treatment with the angiotensin II receptor blocker (ARB) candesartan were evaluated in the macroalbuminuric patients in a randomized double-blinded, cross-over trial where each patient received treatment with placebo, candesartan 8, 16, and 32 mg daily each for 2 months., Results: Overall, 4551 different polypeptides were found in the samples. Urinary polypeptide patterns were comparable in normo- (with and without diabetic retinopathy) and microalbuminuric patients, whereas distinct differences were found in macroalbuminuric patients. Differences in urinary polypeptide patterns between normo- and macroalbuminuric patients permitted the establishment of a "diabetic renal damage" pattern consisting of 113 polypeptides. Eleven of these polypeptides had been sequenced and identified. Candesartan treatment in macroalbuminuric patients significantly changed 15 of the 113 polypeptides in the diabetic renal damage pattern toward levels in normoalbuminuric patients. Change in the diabetic renal damage pattern was not candesartan dose-dependent but individual changes correlated with changes in urinary albumin excretion at each dose level., Conclusion: CE-MS serves as a fast and sensitive tool for identification of biomarkers and urinary polypeptide patterns specific for macroalbuminuric type 2 diabetic patients and may be used to explore and monitor renoprotective effects of ARB.

In stability studies during preclinical drug development, the human antimicrobial peptide hHEM-gamma 130-146 shows progressive N-terminal degradation in plasma. To determine this effect, we developed and validated a selective and quantitative muHPLC-MS/MS procedure for this compound. Following deproteinization by precipitation, reversed-phase separation is performed with a time-saving two-column design online coupled to an ion trap mass spectrometer for electrospray ionization MS detection. Using a linear calibration curve obtained with synthetic external standards ranging nearly two orders of magnitude, we achieved good precision (repeatability and reproducibility: 5-15%), accuracy (-3 to 15%), and ruggedness with a lower limit of quantification at 0.29 microg/ml plasma (0.15 microM). Because of good linearity (r2>0.999), the recovery (84+/-3%) and ion suppression (86+/-4% remaining intensity) were calculated from specifically prepared calibration curves. The developed procedure was applied to human and animal plasma samples. Incubations in the presence and absence of proteinase inhibitors revealed at least an aminopeptidase M activity for the initial N-terminal truncation of tryptophan (W130) and a putative glutaminyl-peptide cyclotransferase activity for the resulting intermediate starting with the bared glutamine residue (Q131). The calculated periods of half-change demonstrated exceeding interspecies variations, whereas the intraspecies variations were only between 20 and 30%. The current procedure is valuable as a generic method for pharmaceutical purposes, and data give important information for further development toward a potential natural drug candidate.

Background: IgA nephropathy (IgAN) is the most common chronic glomerular disease in adults. End-stage renal disease (ESRD) develops in about 30% of the patients. Early intervention and consequent therapy may prevent or at least delay the development of ESRD in these patients. Up to now, the diagnosis could only be achieved with a renal biopsy., Methods: The urine of 45 patients with IgAN was collected and screened for protein/polypeptide patterns with a novel high throughput method, capillary electrophoreses on-line coupled to a mass spectrometer (CE-MS). CE-MS allows the fast and accurate evaluation of up to 2000 polypeptides in one urine sample. The results in IgAN were compared to findings in 13 patients with membranous nephropathy (MN) and 57 healthy individuals., Results: In the patients with IgAN, even when urinary protein excretion was within the normal range of regular tests, the polypeptide pattern in urine differed significantly from that of healthy controls and patients with MN, indicating a specific "IgAN" pattern of polypeptide excretion. Classification regarding discrimination of IgAN from healthy controls and from MN had a sensitivity of 100% and 77%, respectively. Specificity was 90% and 100%, respectively. Compared to patterns established earlier in patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or diabetic nephropathy (DN), sensitivity and specificity were 100%. Treatment of the patients was associated with changes of the pattern, possibly indicating a therapeutic effect., Conclusion: Proteomic analysis with CE-MS coupling permits fast and accurate identification and differentiation of polypeptide patterns in the urine of patients with IgAN, allowing differentiation from healthy controls and, probably, other renal diseases.

We have recently isolated a bioactive, circulating protein of human tazarotene-induced gene-2 (TIG2) as the natural ligand of the orphan receptor ChemR23. Here we describe a simplified method for the isolation of hamster TIG2 protein from Chinese hamster ovary (CHO) cell supernatant. Using a heparin-affinity column followed by two reversed phase chromatography steps resulted in the isolation of pure biologically active material. Two processed bioactive forms of Chinese hamster TIG2 were identified by Edman sequencing and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) mass fingerprint analysis, representing the amino acid residues T20 to F156, and T20 to A155 of the 163 amino acid propeptide. Comparison with the predicted aa-sequence indicates a mutation or modification within the C-terminal end of the peptide.

Sedatives are frequently administered in neonatal intensive care to induce sleep for diagnostic and radiology procedures, calm irritable infants, manage pain-related agitation, and enhance ventilation. The pharmacology and side effects of sedatives commonly used with neonates will be reviewed and placed within the context of their potential effect on neonatal development. Alternative caregiving strategies to minimize or eliminate the need for sedation will be discussed.

Proteinase inhibitors are important negative regulators of proteinase action in vivo and are thus involved in several pathophysiological processes. Starting with the isolation of two new peptides from human blood filtrate, we succeeded in cloning a cDNA encoding the precursor protein for a novel 15-domain Kazal-type-related serine proteinase inhibitor. Two of the 15 domains almost exactly match the Kazal-type pattern, whereas the other 13 domains exhibit only four instead of six cysteine residues. Since the corresponding gene is expressed in several lympho-epithelial tissues, we termed this inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). For three of the 15 LEKTI domains, we demonstrated a significant trypsin-inhibiting activity. Recent results of another group show a relation between mutations within the LEKTI gene and the severe congenital disorder Netherton syndrome. In this review article, we give an overview of the already known data on the structure, processing, gene expression, and pathophysiological role of LEKTI.

A specific and saturable interaction between 125I-gastrin and eosinophils was discovered in autoradiographs of human gastric mucosal tissue and confirmed in isolated and enriched preparations of WBC's. Gastrin displaced 125I-gastrin from eosinophils in a dose-dependent manner with a D50 = 11 uM. Scatchard analysis of the saturation curve indicated a single binding site of low affinity (Kd = 4.14 uM) and high capacity (Bmax = 430 umoles/mg protein). The gastrin binding protein was localized to the granular core of the eosinophil and found to have a molecular weight of approximately 15 kDa following chemical crosslinking of radioligand to granules and SDS/PAGE. Based on its molecular weight and granular location and the charge characteristics of gastrin, the gastrin binding protein in the human eosinophil is most likely major basic protein. In vivo this interaction might act to limit the cytotoxic potential of MBP on tissues and/or attentuate gastrin concentrations thereby helping regulate gastric acid secretion and mucosal growth.

Developmental care has been widely accepted and implemented in neonatal intensive care units across the country. Its proponents suggest that individualized developmental care is effective in reducing infant morbidity and length of hospital stay and improving neurodevelopmental outcomes. Although individual components of developmental care have been researched in more depth, few studies have examined a total developmental care protocol. This article critically examines the research base on individualized developmental care and discusses implications for clinical practice and future research.

The binding of biologically active 125I-labeled derivatives of the C-terminal octapeptide of cholecystokinin (125I-CCK8) and gastrin (125I-G) to dispersed guinea pig fundic glands were compared at 24 degrees C. Although both peptides share the same C-terminal pentapeptide sequence, differences were found in the amount of each radioligand bound to fundic glands, their dissociation behavior, and their Scatchard plots. However, each peptide was able to displace the other radioligand from the glands at nM concentrations which indicated that both peptides bound to the same site. The different binding characteristics observed for 125I-G and 125I-CCK8 most likely resulted from the different dissociation rates of each peptide.

High-pressure liquid chromatography was used to separate the following steroidal alkaloids: tomatidine, solanidine, solasodine, rubijervine, veratramine and jervine. The method was used to prepare crystalline solanidine from a crude mixture of aglycones obtained from Solanum chacoense, and to separate radioactive solanidine from extracts of potato plants fed with [4-C]cholesterol.

Using electric eel acetylcholinesterase (AChE) which was either membrane-bound (AChEm) or solubilized (AChEs), similar kinetics were seen in the absence of inhibitor or in the presence of edrophonium, trimethylammonium ion or paraoxon. Thus, both forms of the enzyme appear to behave similarly toward various inhibitors. However, in the presence of a probe sensitive to allosteric effects or changes in membrane fluidity, the two forms exhibit altered behavior. In the presence of F-, the relative rate of substrate hydrolysis by AChEm was reduced more rapidly than with AChEs, whether or not paraoxon was present. When inhibition by paraoxon (10(-7)-10(-4) M) was studied in the presence of F-, AChEs had a Hill coefficient of 1.0, whereas with AChEm the Hill coefficient changed from 0.8 to 1.5.