Biomedical subjects

Catherine Temelcos

Publications and source records attributed to Catherine Temelcos.

3 recordsLinked to original sources

PubMed2005

Could inguinal hernia be treated medically?

Inguinal hernia is the most common congenital anomaly requiring surgical correction. The cause of the hernia is, most commonly, persistence of the processus vaginalis. Study of testicular descent in rodents has revealed a role for the genitofemoral nerve and calcitonin gene-related peptide (CGRP). Since the testis cannot descend without the processus vaginalis, we wondered whether both descent and hernia closure might be regulated by the same mechanism. Therefore, we tested the idea that CGRP might be active in closure of the inguinal hernia. Using hernial sacs removed at herniotomy operation, fusion of the hernial surfaces was induced by CGRP, but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone. Hepatocyte growth factor also caused peritoneal obliteration in vitro. We propose that obliteration of the processus vaginalis is under the control of molecules released from the genitofemoral nerve, and that a chemical treatment of inguinal hernia is at least theoretically possible.

Animals↗

PubMed2004

Ontogeny of the VATER kidney in a rat model.

By exposing rat fetuses to adriamycin prenatally, a rat model of VATER association has been created. Absence of the fetal bladder is prominent and the kidneys show features of chronic obstruction with hydronephrosis/hydroureter, loss of parenchyma, fewer glomeruli, and less differentiation. The aim of this study was to elucidate this rat model, to determine exactly when the changes in the kidneys develop, hopefully thereby to expand our understanding of congenital obstructive uropathy. Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin on days 6-9 of gestation. The control group received saline. Fetuses were recovered on gestational days (GDs) 20, 19, 18, 17, 16, 15, 14, 12, and 10 (total, 120 control, 121 treated). Macroscopic features were determined. Serial sections were then taken and stained with hematoxylin and eosin. Comparisons were made under light microscopy. The metanephric kidney first became apparent at GD12. The development of the control and treated kidneys appeared similar till GD18. Beyond this day, the treated kidneys exhibited increasing degrees of distension of Bowman's capsule, ducts, and subsequently pelvis and ureter. There were fewer levels of glomeruli, which were also less differentiated. Less differentiation was also noted in the medulla, and with time this became thin in comparison to the control kidneys. By GD20, the renal pelvis was grossly dilated with a blunted papilla, and the renal parenchyma was thin. Prenatal exposure of rat fetuses to adriamycin results in kidneys that are chronically obstructed, as the majority of the fetuses show absence of the bladder. Absence of renal dysmorphology until GD18, when urine is first produced, suggests strongly that the effect of adriamycin on the kidney is indirect, via agenesis of the bladder and secondary to backpressure from early urine production. This is a unique, simple, and reliable model of fetal obstructive uropathy and will be very useful to facilitate further investigation into its pathophysiology and to explore new treatment options.

Abnormalities, Drug-Induced↗

PubMed2004

Renal abnormalities in rat fetuses exposed to doxorubicin.

PURPOSE: A rat model of the VATER (vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, renal defects and radial limb dysplasia) association was created by exposing fetuses to doxorubicin early in gestation. Most fetuses had an absent bladder with ureters that were grossly dilated. We determined the effect of this absent bladder on kidneys development, particularly whether dysplasia was evident. MATERIALS AND METHODS: Nine timed pregnant rats were injected intraperitoneally with doxorubicin at a dose of 2 mg/kg body weight on days 6 to 9 of gestation. The control group of 3 rats received saline. Fetuses were recovered on day 21 and examined macroscopically. Quantitative measurements were taken of renal wet and dry weights, renal length and ureteral diameter. Serial sections were then taken and stained alternately with hematoxylin and eosin or trichrome. The kidneys were compared under light microscopy. Comparisons between control and treated groups were made with the Student t test. RESULTS: An absent bladder was confirmed in 50 of the 55 fetuses (91%). In most fetuses the kidneys were correctly located, although they were hydronephrotic and poorly developed. This finding was confirmed quantitatively with significant differences in treated and control fetuses in renal length (5.24 vs 4.13 mm, p <<0.01) and in the ratio of wet renal weight to body weight and dry weight (2.7 vs 3.4 mg, p <<0.01). Dilated, tortuous ureters were found bilaterally in most cases. Microscopically the kidneys had abnormal architecture and were less mature than in controls. Nephron induction was poor with abnormal configurations. Tubular differentiation was decreased and the medulla was thin and less cellular than in controls. Dilatation occurred mainly in the collecting system and ducts/tubules. There was no collagen deposition/fibrosis or aberrant tissue. CONCLUSIONS: In this rat model the kidneys are exposed to obstruction early in development since the bladder does not form. The resulting kidneys are hydronephrotic with decreased parenchyma and poor differentiation. However, there is no fibrosis or aberrant tissue.

Abnormalities, Drug-Induced↗