Leprecan distribution in the developing and adult kidney.

The temporal and spatial deposition of extracellular matrix proteins is critical for nephrogenesis and glomerular maturation. We previously characterized leprecan as a novel chondroitin sulfate proteoglycan which has been recently shown to have prolyl hydroxylase activity. In this study, we examine the distribution of leprecan during nephrogenesis and after a hypertrophic stimulus to the adult kidney. During development, leprecan was localized to mesenchymal aggregates, early comma- and S-phase structures as determined by immunohistochemistry and in situ hybridization. Leprecan mRNA was increased in cells around the vascular cleft of the S- and comma-phase glomeruli. Expression was found in podocytes, mesangial cells, and parietal epithelial cells of loop-phase glomeruli. Leprecan mRNA was substantially decreased in the glomeruli of the adult kidney compared to the developing kidney with a uniform distribution between the glomeruli and the tubules. Within adult glomeruli, leprecan was found in the mesangium mesangial matrix, podocytes, and in Bowman's capsule. In response to glomerular hypertrophy, produced by unilateral nephrectomy, leprecan synthesis was increased in the adult kidney. We suggest that the regulated expression of leprecan during glomerular development or hypertrophy coupled with its reported prolyl hydroxylase activity plays a role during basement membrane assembly.

Peripheral administration of urocortin suppresses operant responding for food reward.

The effects of peripheral systemic administration of urocortin on operant responding to obtain food were investigated using three separate concentrations. The drug was administered intraparitoneally at a concentration of 10 microg/ml/Kg, 5 microg/ml/Kg, and 0 microg/ml/Kg suspended in saline at a volume of 1 ml/Kg to Sprague-Dawley rats fifteen minutes prior to being exposed to an operant bar press task. Eleven subjects were used, each receiving a single injection of each concentration on separate days with the order of treatment counterbalanced. The results indicated that the administration of urocortin in a dose dependent manner reduced responding of food deprived subjects for a food reward in a thirty minute session. These data indicated that the peripheral administration of urocortin reduced the motivation of food deprived subjects to respond.

A prospective study of methylprednisolone and prednisone as immunosuppressive agents in clinical renal transplantation.

A prospective double blind crossover study was carried out in 65 patients comparing methylprednisolone (Medrol) and prednisone as immunosuppressive agents in clinical renal transplantation to determine their relative merits vis-a-vis graft survival, hypertension, weight gain, sepsis and patient preference in the posttransplant period. Patients receiving renal allografts were randomly assigned to receive initial treatment with one of the drugs. Once maintenance doses were employed, the drug was switched for a 3-month period. There was no difference in overall graft survival at 1 year, 68% versus 56% (p greater than 0.4), for the two patient groups. Likewise, there was no difference in blood pressure during the maintenance therapy crossover period, mean BP 129/86 during Medrol therapy and 129/86 during prednisone therapy. Overall weight gain was not statistically different with the two drugs, 3.8 kg with prednisone and 2.3 kg with Medrol, p greater than 0.1. However, when Medrol was used in the late posttransplant period, the patient had a significantly smaller weight gain, 0.95 kg versus 3.5 kg with prednisone, p greater than 0.05. The incidence of bacterial sepsis was significantly greater (p less than 0.02) during the early posttransplant period in those patients treated with Medrol. Finally, the majority of patients (65%) had no preference for either drug. Of those with a preference, the majority (69%) preferred Medrol. We conclude that therapy with Medrol does not offer superior graft survival, less hypertension or overriding patient preference but does apparently lead to an increased incidence of bacterial sepsis in the early posttransplant period. Thus it appears that prednisone is the initial drug of choice as an immunosuppressive steroid in clinical renal transplantation.

Successful immunosuppression of renal allograft recipients with alternate day steroid therapy.

Twenty-five renal transplant recipients have been treated long-term with immunosuppressive therapy with conversion from a daily dose to an every other day dose of steroids in conjunction with daily administration of Imuran. The patients were selected by having stable grafts for 6 to 9 months prior to conversion, not by the presence of steroid-induced complications. Alternate day steroid administration has continued to provide successful immunosuppression in that only of 25 patients (4%) has had any evidence of renewed rejection activity during a treatment interval of 7--95 months, median 22 months and mean 28 months. One graft was lost to an acute rejection reaction that occurred in association with a flu-like syndrome 8 months after the conversion was started. It is concluded that in the patient with documented stability of the graft, every other day steroid administration is a successful immunosuppressive regimen.

Foley catheter tip cultures: a valuable diagnostic aid in the immunosuppressed patient.

Cultures of forty-three Foley catheter tips from immunosuppressed renal transplant patients have been analyzed and correlated with the subsequent development of urinary tract infection. Fifteen cultures produced no growth and two showed only coagulase-negative staphylococci; none of these patients subsequently developed a urinary tract infection. Twenty-four of the cultures showed at least one organism known to be a frequent urinary pathogen; sixteen (67 per cent) of these patients developed a urinary tract infection within ten days of the culture, and all sixteen had an infection caused by an organism present on the Foley tip. None of the organisms were identified by simultaneous catheter specimen urine cultures. Foley tip cultures in the immunosuppressed renal transplant patients are predictive of urinary sepsis and diagnostic of the causative organism.