The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-Cre, PTEN knockout mice.

BACKGROUND: Elevated insulin-like growth factor-I (IGF-I) serum levels and phosphatase and tensin homolog (PTEN) loss are prostate cancer (PCa) risk factors that enhance androgen-responsive and castration-resistant PCa xenografts growth. METHODS: The impact of suppressed growth hormone (GH)/IGF-I levels on neoplastic initiation of PTEN-deficient prostate epithelia was assessed histologically and by epithelial-to-mesenchymal marker expression in Ghrhr D60G homozygous (lit/lit) and heterozygous (lit/+) pbARR2-Cre, PTEN(fl/fl) (PTEN-/-) mice. How suppressed GH/IGF-I levels impacted growth of PTEN-/- mouse-derived prostate cells (MPPK) was examined by growth and survival signaling of cells cultured in lit/+ or lit/lit serum. RESULTS: Body weight, prostate weight and serum GH and IGF-I levels were reduced in lit/lit relative to lit/+ PTEN-/- littermates. While the anterior lobes of lit/+ PTEN-/- prostates consistently presented swollen, indicative of ductal blockage, the degree of prostatic dysplasia in 15- and 20-week-old lit/lit and lit/+ PTEN-/- mice was indistinguishable as measured by normalized prostatic weight, tissue histology, or probasin, PSP94, E-cadherin, N-cadherin and vimentin expression. However, growth and AKT activation of MPPK cells was decreased when cultured in lit/lit serum as compared with lit/+ serum and restored in lit/lit serum supplemented with IGF-I and, to a lesser extent, GH. CONCLUSIONS: These results suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germline variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that these factors may affect the progression of dysplastic phenotype and supports previous studies, indicating that the GH/IGF milieu does impact the growth of PTEN-deficient dysplastic prostatic cells once transformed.

Effect of glutamate-aspartate reperfusion on postischemic neonatal myocardium.

OBJECTIVE: We postulated that L-glutamate- and L-aspartate-enriched perfusate would improve functional recovery of postischemic neonatal rabbit hearts. METHODS: Isolated working neonatal rabbit hearts were perfused with Krebs-Henseleit buffer and then subjected to 1 hour of hypothermic cardioplegic arrest with St. Thomas' Hospital solution. Hearts were then reperfused with L-glutamate- and L-aspartate-enriched (20 mmol/L) Krebs-Henseleit buffer (AA-enriched Krebs-Henseleit buffer). Hearts reperfused with Krebs-Henseleit buffer alone acted as controls (experiment A). Another group of hearts underwent a similar protocol but were reperfused with the AA-enriched Krebs-Henseleit buffer with correction of the sodium content (experiment B). RESULTS: Hearts reperfused with AA-enriched Krebs-Henseleit buffer showed a significant decrease in aortic flow at both 15 (p = 0.04) and 30 (p = 0.025) minutes compared with controls. Arrhythmias were frequent. Sodium content of the AA-enriched Krebs-Henseleit buffer was 174 +/- 0.5 mmol/L. In experiment B, hearts reperfused with the AA-enriched Krebs-Henseleit buffer with correction of the sodium content exhibited no difference in aortic flow and cardiac output at either 15 or 30 minutes (p = 0.95 and 0.5 and 0.48 and 0.78, respectively) compared with controls. No arrhythmias were observed. The sodium content of the AA-enriched Krebs-Henseleit buffer was 146 +/- 0.7 mmol/L. CONCLUSIONS: A beneficial effect on functional recovery of neonatal hearts reperfused with AA-enriched Krebs-Henseleit buffer was not demonstrated.

Laboratory variables of bladder autoaugmentation in an animal model.

OBJECTIVES: Evaluations of the functional, radiologic, and pathologic outcomes of autoaugmentation by two surgical techniques (vesicomyectomy versus vesicomyotomy) were compared. Autoaugmentation or vesicomyotomy is being increasingly considered as a simplified method of bladder augmentation in the hypertonic decreased-capacity bladder. METHODS: In a series of 35 laboratory sessions, creation of an animal model approximating the small-capacity hypertonic bladder was achieved. Sixteen vesicomyotomies and 16 vesicomyectomies were performed on the 32 stabilized one-third reduced bladders. Three stabilized one-third reduced bladders were used as controls. RESULTS: Radiologic studies show a large diverticulum. A 17.2% net increase in surface area was achieved, compared with the reduced bladder, at the time of pathologic examination. Functional capacity was increased by 43.5% on urodynamic studies, and leak point pressure was decreased by 48.1%. Histologic and morphometric examinations of the autoaugmentation area showed a few muscle fibers with serosal deposition of collagen. There was less muscle ingrowth at the periphery of the autoaugmentation site utilizing vesicomyectomy. CONCLUSIONS: There was no statistical difference between vesicomyotomy and vesicomyectomy with respect to radiologic, pathologic, or urodynamic outcome.

Bladder autoaugmentation by vesicomyotomy in the pediatric neurogenic bladder.

OBJECTIVES: The authors describe the procedure of bladder autoaugmentation by vesicomyotomy in 12 pediatric patients with neurogenic bladders. METHODS: Indications for augmentation included low-capacity, high-pressure bladders with incontinence despite maximal anticholinergic therapy. Clean intermittent catheterization was successfully reinstituted postoperatively and no patient has subsequently required enterocystoplasty. RESULTS: There were no major complications and eight patients underwent concurrent procedures on the bladder. Urodynamic studies revealed a mean increase in capacity of 40% and a mean decrease in leak point pressure of 33% compared with preoperative values. CONCLUSIONS: Early clinical experience would suggest that vesicomyectomy (excision of released detrusor) offers no advantages over vesicomyotomy in pediatric patients. Vesicomyotomy (simple incision into detrusor) proved to be a simple technique that could be safely performed in pediatric patients.

A comparison of two continent catheterizable vesicocutaneous techniques.

In a rabbit model we describe and compare two continent catheterizable diversion techniques for which the bladder is intact and the stoma is situated in the lower abdomen. Both mechanisms are formed from a short segment of ileum; one utilizes the principles of the encircling loop technique as described by Koff and the second, the Kock principle (intravesical nipple). Both models were evaluated for the following parameters: ease of catheterization (87%, 79% respectively), continence (91%, 86% respectively), and ease of construction. We present evidence that both techniques are applicable to the clinical setting.

Myocardial oedema and ventricular function after cardioplegia with added mannitol.

Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L-3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest.