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1.
Urologie ; 61(6): 657-659, 2022 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-35171299

RESUMEN

Alveolar ecchinococcosis, caused by the fox tapeworm (echinococcosus multilocularis), is in principle a lethal illness. We report on a 31-year-old man presenting with an unclear epididymal tumor, in whom further examinations revealed multiple and extended partially cystic, partially solid intra-abdominal tumors. Diagnosis was achieved histologically by percutaneous biopsy of a spleen lesion and serologically. As a surgical resection of the lesions was not feasible, therapy with albendazol was initiated.


Asunto(s)
Cestodos , Equinococosis , Echinococcus multilocularis , Adulto , Animales , Equinococosis/diagnóstico , Humanos , Masculino
2.
Urologe A ; 59(10): 1231-1236, 2020 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-32377765

RESUMEN

BACKGROUND AND OBJECTIVES: Eye lens radiation exposure during fluoroscopy-guided interventional procedures may result in occupational radiation-induced cataracts. We evaluated the eye lens radiation doses and the protective effect of X­ray protective visors during ureteroscopic procedures. MATERIALS AND METHODS: Eye lens doses were measured in front of and behind X­ray protective visors using eye lens dosemeters during ureteroscopic procedures done by 4 different endourologic surgeons within a 12-week period. Background radiation dose, simultaneously measured with transport dosemeters, was subtracted. Measured eye lens doses below the detection limit of the eye lens dosemeters were adjusted to the detection limit of 0.028 mSv. Correlating the eye lens doses (ELD) to the dose-area-product (DAP) an ELD/DAP ratio was calculated. Applying this ELD/DAP ratio the potential reduction of the eye lens radiation dose was retrospectively calculated for all ureteroscopic procedures done within one year. RESULTS: Within the 12-week period 76 ureteroscopies were done by the 4 endourologic surgeons. The accumulated eye lens radiation dose was 0.796 mSv in front of the X­ray protective visors, and 0.338 mSv behind the X­ray protective visors. Thus, the eye lens radiation exposure was reduced to at least 42% by using X­ray protective visors. Considering the 215 documented ureteroscopies in our clinic in the year before starting the study, occupational radiation exposure to the eye lens would have been reduced by X­ray protective visors from 4.090 to 1.737 mSv. CONCLUSION: X­ray protective visors can effectively reduce the radiation exposure to the eye lens during fluoroscopy-guided endourologic procedures and should be used especially by high-volume endourologic surgeons.


Asunto(s)
Cristalino , Exposición a la Radiación , Dosis de Radiación , Exposición a la Radiación/análisis , Exposición a la Radiación/prevención & control , Estudios Retrospectivos , Ureteroscopía , Rayos X
3.
J Comp Pathol ; 158: 71-76, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29422319

RESUMEN

Within 4 weeks, five cats with skin lesions affecting the hindlimbs and mainly consisting of oedema, hyperaemia and plaque-like alterations were presented to the same veterinary clinic. The cats were suffering from lameness, trauma, renal insufficiency or complicated tail amputation. Although the lesions seemed unusual for a poxvirus infection, microscopical examination of biopsy samples or specimens taken during necropsy examination revealed ballooning degeneration of keratinocytes with eosinophilic, cytoplasmic inclusion bodies indicative of an orthopoxvirus infection. Cowpox virus infection was verified using immunohistochemistry and virus isolation. Molecular analysis revealed identical haemagglutinin gene sequences in four cases and spatiotemporal circumstances in some cases pointed to hospital-acquired transmission. Unusual manifestations of feline cowpox may have an unexpected risk for human infection.


Asunto(s)
Enfermedades de los Gatos/virología , Viruela Vacuna/veterinaria , Animales , Enfermedades de los Gatos/patología , Gatos , Virus de la Viruela Vacuna
4.
Urologe A ; 55(3): 364-9, 2016 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-26228592

RESUMEN

BACKGROUND AND OBJECTIVES: Eye lens radiation exposure during radiologically-guided endoscopic procedures may result in radiation-induced cataracts; therefore, we investigated the ocular radiation exposure during ureteroscopy on a phantom model. MATERIALS AND METHODS: Using an Alderson phantom model and eye lens dosimeters, we measured the ocular radiation exposure depending on the number of X-ray images and on the duration of fluoroscopic imaging. The measurements were done with and without using a face protection shield. RESULTS: We could demonstrate that a significant ocular radiation exposure can occur, depending on the number of X-ray images and on the duration time of fluoroscopy. Eye lens doses up to 0.025 mSv were recorded even using modern digital X-ray systems. Using face protection shields this ocular radiation exposure can be reduced to a minimum. CONCLUSION: The International Commission on Radiological Protection (ICRP) recommendations of a mean eye lens dosage of 20 mSv/year may be exceeded during repeated ureteroscopy by a high volume surgeon. Using a face protection shield, the eye lens dose during ureteroscopy could be reduced to a minimum in a phantom model. Further investigations will show whether these results can be transferred to real life ureteroscopic procedures.


Asunto(s)
Dispositivos de Protección de la Cabeza , Cristalino/efectos de la radiación , Exposición a la Radiación/análisis , Protección Radiológica/instrumentación , Radiografía Intervencional/efectos adversos , Ureteroscopía/efectos adversos , Absorción de Radiación , Catarata/etiología , Catarata/prevención & control , Humanos , Fantasmas de Imagen , Exposición a la Radiación/prevención & control , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Radiometría/métodos
5.
Urologe A ; 52(1): 60-4, 2013 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-23052980

RESUMEN

BACKGROUND: We determined the intraoperative patient radiation exposure during ureteroscopic extraction of ureteral or renal stones. MATERIAL AND METHODS: The investigation was carried out in 215 patients who underwent ureteroscopy for ureteral or renal stone extraction. Radiation exposure was measured as dose-area product (DAP) within the X-ray beam. The effective abdominal dose was calculated using the specific conversion factor of 0.00323 mSv/µGy×m². RESULTS: Depending on the stone location (i.e. ureter or kidney), the type of ureteroscopy (i.e. semirigid or flexible) and type of stone removal (i.e. simple stone extraction or intracorporeal laser lithotripsy), the intraoperative patient radiation exposure (effective dose ED) ranged from 0.67 mSv (DAP 221.9 µGy×m²) to 2.23 mSv (DAP 744.2 µGy×m²). CONCLUSION: Patient radiation exposure during ureteroscopic stone extraction is comparable to patient radiation exposure using plain film urography or low-dose non-contrast-enhanced computed tomography for diagnosis of urolithiasis.


Asunto(s)
Dosis de Radiación , Radiografía Intervencional/estadística & datos numéricos , Radiometría/estadística & datos numéricos , Ureteroscopía/estadística & datos numéricos , Cálculos Urinarios/diagnóstico , Cálculos Urinarios/cirugía , Adolescente , Adulto , Anciano , Carga Corporal (Radioterapia) , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Cálculos Urinarios/epidemiología , Adulto Joven
6.
Horm Metab Res ; 43(9): 601-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21823054

RESUMEN

Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat metabolism and their inhibition has been postulated to be beneficial for the treatment of the metabolic syndrome by decreasing ectopic fat accumulation. In order to validate this approach pharmacologically, we characterized the chronic effect of the small molecule ACC1/2 inhibitor SAR210 in 2 rodent models of fatty liver. Chronic administration of SAR210 increased serum ketone levels in both diet-induced obese mice and female ZDF rats. The inhibitor neither reduced hepatic triglycerides nor influenced body weight in either diet-induced obese mice or female ZDF rats. Thus, chronic pharmacological inhibition of ACC1/2 stimulated fat oxidation, which was, however, not sufficient to reduce hepatic triglycerides.


Asunto(s)
Acetil-CoA Carboxilasa/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Grasas/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado/metabolismo , Animales , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacocinética , Hígado Graso/enzimología , Hígado Graso/metabolismo , Femenino , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Wistar
7.
J Gen Virol ; 92(Pt 8): 1906-1916, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21593276

RESUMEN

Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing disease of the central nervous system in central Europe. In this study, 61 TBEV E gene sequences derived from 48 isolates from the Czech Republic, and four isolates and nine TBEV strains detected in ticks from Germany, covering more than half a century from 1954 to 2009, were sequenced and subjected to phylogenetic and Bayesian phylodynamic analysis to determine the phylogeography of TBEV in central Europe. The general Eurasian continental east-to-west pattern of the spread of TBEV was confirmed at the regional level but is interlaced with spreading that arises because of local geography and anthropogenic influence. This spread is reflected by the disease pattern in the Czech Republic that has been observed since 1991. The overall evolutionary rate was estimated to be approximately 8×10(-4) substitutions per nucleotide per year. The analysis of the TBEV E genes of 11 strains isolated at one natural focus in zdár Kaplice proved for the first time that TBEV is indeed subject to local evolution.


Asunto(s)
Vectores Arácnidos/virología , Virus de la Encefalitis Transmitidos por Garrapatas/clasificación , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Ixodes/virología , Filogenia , Animales , Secuencia de Bases , República Checa , Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Encefalitis Transmitida por Garrapatas/virología , Evolución Molecular , Alemania , Humanos , Ratones , Datos de Secuencia Molecular , Filogeografía , Proteínas Virales/genética
8.
Urologe A ; 46(12): 1710-4, 2007 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-17932642

RESUMEN

PURPOSE: We investigated the feasibility of using flat panel volumetric computer tomography (fpVCT) for the detection of orthotopically implanted renal carcinomas in nude mice. MATERIALS AND METHODS: One million renal cell carcinoma cells [A-498 line (Braunschweig, Germany), in 0.2 ml phosphate-buffered solution (PBS), pH 7.4] were injected into the left kidney of each of the eight nude mice. Each mouse was imaged twice (12 and 16 weeks after implantation) with fpVCT (GE prototype with circular gantry with two 1024 x 1024, 200 microm pixel size, aSi/CsI flat panel detector) after injection of 200 microl contrast medium to check for tumour spread. After 16 weeks the mice were killed and dissected, and the imaging findings in liver, kidneys and lung were compared with the macroscopic findings. RESULTS: No local evidence of tumour or of metastatic spread was seen on fpVCT after 12 weeks in any of the mice. After 16 weeks fpVCT revealed tumour growth in 6 of the 16 kidneys. Two mice had each developed a multifocal renal cell carcinoma and one mouse, a bilateral renal tumour manifestation. In one mouse liver metastases were seen. The fpVCT findings correlated well with the observations recorded in the pathological examination. CONCLUSION: fpVCT is an innovative and noninvasive imaging procedure that can be used for longitudinal investigation of tumour progression following orthotopic implantation of renal cell carcinoma to small animals. The use of a system of this kind will make a decisive contribution to reducing the number of animals used in experimental test projects.


Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Neoplasias Renales/diagnóstico por imagen , Animales , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Progresión de la Enfermedad , Estudios de Factibilidad , Riñón/diagnóstico por imagen , Riñón/patología , Neoplasias Renales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias/patología , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/patología
9.
Aktuelle Urol ; 38(1): 46-51, 2007 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-17290329

RESUMEN

BACKGROUND: There is controversy about preoperative chemotherapy in the treatment of Wilms' tumor. The perioperative morbidity plays a key role in this discussion. Therefore, risk factors of perioperative complications were analysed in our series of patients with Wilms' tumor with a special focus on the effects of preoperative chemotherapy. PATIENTS AND METHODS: Case histories of 37 patients [mean age 3.9 (range: 0.6 - 14) years] were retrospectively analysed concerning follow-up, clinical and histopathological stage, size of the primary tumor, as well as duration and extent of preoperative chemotherapy. RESULTS: 35 patients underwent radical nephrectomy, 2 patients had organ-sparing surgery because of bilateral involvement. The mean maximal tumor diameter was 9.5 cm (range: 4 - 24 cm). 11/37 patients had no or shortened preoperative chemotherapy. 6/37 patients (16.2 %) had perioperative complications. There was one intraoperative tumor rupture, 4 small bowel obstructions, 1 pancreatitis. All complications occurred in patients of clinical stages III and IV, maximal tumor diameter > 10 cm after unusually extended operative procedures. 4 patients showed only poor response to preoperative chemotherapy. Patients with doxorubicin pre-treatment showed a higher risk of postoperative small bowel obstruction. CONCLUSIONS: The risk of perioperative complications was correlated with the local extent of the primary tumor and was higher with those requiring more extensive surgical interventions. The influence of preoperative chemotherapy on the complications rate is inconstant. Considering a good response of the primary tumor, the complication rate will be decreased. However, the comorbidity of more intense preoperative chemotherapy in patients of stage IV may contribute to a higher risk of surgical complications.


Asunto(s)
Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Terapia Neoadyuvante , Complicaciones Posoperatorias/etiología , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/cirugía , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Terapia Combinada , Dactinomicina/efectos adversos , Dactinomicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Obstrucción Intestinal/inducido químicamente , Neoplasias Renales/patología , Masculino , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Vincristina/efectos adversos , Vincristina/uso terapéutico , Tumor de Wilms/patología
11.
Urologe A ; 45(7): 852-7, 2006 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-16683155

RESUMEN

INTRODUCTION: In bilateral VUR, Cohen cross-trigonal ureteric reimplantation is a popular but also controversial surgical approach. We present our own experience in a retrospective analysis. PATIENTS AND METHODS: Between 1990 and 2005, 41 children (26 girls, 15 boys) with bilateral reflux [92 renal units (RU)] underwent ureteric reimplantation. The mean age was 4.5 (0.3-12) years. Eight patients had ureteral duplication (six unilateral, two bilateral); 12 of 41 patients had no intraoperative ureteral stenting. Seven patients had prior surgery for VUR. A successful result was defined as absence of VUR, significant UVJ obstruction, or voiding dysfunction throughout the follow-up. RESULTS: The mean follow-up was 7.8 (0.5-15) years. Eight patients (19.5%) had 13 complications. One patient had an intraoperative small bowel lesion (2%). Six patients (14.6%) had UTI. Four patients (9.8%) showed transient UVJ obstruction. Three required a temporary percutaneous nephrostomy. Two of these patients had no intraoperative ureteral stenting. Recurrence of VUR was found in 2 patients (4.8%) and 2/92 RU (2.2%), respectively. Complications were more frequent in high-grade VUR, ureter duplex, or unstented ureteral reimplantation. Prior surgery for VUR did not influence the postoperative outcome. Postoperative voiding disorders were not observed. CONCLUSIONS: Two unilateral recurrences of VUR were observed, requiring a reoperation in one patient. A reoperation for UVJ obstruction was not necessary. Related to 92 RU the surgical success rate was 97.8%. Intraoperative ureteral stenting has to be considered with respect to the current discussion of shortening inpatient procedures. In our experience, the perioperative risk was elevated in patients with high-grade VUR or ureteral duplication.


Asunto(s)
Politetrafluoroetileno/uso terapéutico , Reimplantación/métodos , Uréter/cirugía , Ureterostomía/instrumentación , Ureterostomía/métodos , Reflujo Vesicoureteral/cirugía , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Reimplantación/instrumentación , Resultado del Tratamiento
12.
Urologe A ; 43(8): 989-91, 2004 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-15205740

RESUMEN

Ectopic ureters associated with dysplastic kidneys remain a diagnostic dilemma. Ultrasound, endoscopy as well as intravenous urography do not always show correct urinary tract morphology and function. We report the case of a 6-year-old girl with continuous urine dribbling to demonstrate the diagnostic value of MR urography.


Asunto(s)
Coristoma/diagnóstico , Imagen por Resonancia Magnética/métodos , Riñón Displástico Multiquístico/diagnóstico , Uréter , Enfermedades Ureterales/diagnóstico , Niño , Coristoma/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Riñón Displástico Multiquístico/complicaciones , Enfermedades Ureterales/complicaciones
14.
J Pediatr Surg ; 37(5): E15, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11987115

RESUMEN

BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy consists of ureteral reimplantation. However, in case of bilateral single ectopic ureters, subsequent malformation of the bladder trigone and bladder neck may result in additional voiding dysfunction, and ureteral reimplantation alone may not solve the urologic problems. METHODS: The authors report their experience with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral reimplantation in early childhood and who did not gain adequate bladder control during following years. RESULTS: Videourodynamic evaluation was done in both girls. No bladder overactivity was found during the urodynamic studies. However, cystography showed a widely open bladder neck during filling with no sufficient bladder neck closure shown by urethral pressure profile studies. When blocking the bladder outlet by balloon catheters, adequate bladder filling volume was achieved. Incontinence was cured by implantation of an AMS 800 artificial sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too young for sphincter implantation and is waiting for surgery within the next years. CONCLUSION: Insufficient development of trigone and bladder neck with subsequent urinary incontinence has to be kept in mind when deciding on surgical procedures in children with bilateral single ectopic ureters.


Asunto(s)
Reimplantación , Uréter/anomalías , Uréter/cirugía , Anomalías Múltiples/cirugía , Femenino , Humanos , Recurrencia , Vejiga Urinaria/anomalías , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control , Infecciones Urinarias/etiología , Infecciones Urinarias/prevención & control , Urodinámica , Grabación en Video
15.
Klin Padiatr ; 213(6): 314-6, 2001.
Artículo en Alemán | MEDLINE | ID: mdl-11713707

RESUMEN

BACKGROUND: Ectopic ureter - especially in a duplicated collecting renal system - is a specific cause of incontinence in young girls. Although the symptom of continuous dribbling of urine is characteristic for this malformation, diagnosis is often delayed, as the possibility of ectopic ureters is not considered in treating girls with delayed toilet training. CASE REPORT: We present the case of a young girl with a variety of unnecessary invasive diagnostic and therapeutic procedures due to a misunderstood "enuresis", before incontinence was cured by upper pole heminephrectomy. CONCLUSIONS: Girls, who never have been dry and who loose urine all the time do have an ectopic ureter, unless evidence to the contrary has been put forward. Only considering the possibility of ectopic ureters will avoid unnecessary diagnostic and therapeutic procedures in these girls.


Asunto(s)
Enuresis/etiología , Uréter/anomalías , Incontinencia Urinaria/etiología , Vagina/anomalías , Niño , Diagnóstico Diferencial , Enuresis/cirugía , Femenino , Humanos , Riñón/anomalías , Nefrectomía , Ultrasonografía , Incontinencia Urinaria/cirugía , Urografía
16.
Microvasc Res ; 62(2): 172-8, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11516246

RESUMEN

The surgically induced split hydronephrotic kidney has been generally accepted as a valid model for the assessment of renal microcirculation by means of intravital microscopy. Whereas nearly all previous work on this issue has been done with a transillumination technique, we used an epiillumination model that is suitable for investigation of microvascular perfusion in both normal and hydronephrotic kidneys without surgical manipulation of the ureter. By means of the congenital unilaterally hydronephrotic Tauchi rat, microcirculation of the hydronephrotic and that of the nonhydronephrotic kidney were compared. For that purpose both the hydronephrotic and the nonhydronephrotic kidneys of Tauchi rats were exteriorized on a specially designed microscopy stage. After injection of FITC-dextran and rhodamine 6G, microvascular perfusion was assessed in both kidneys. The new model allowed visualization of arterioles, capillaries, and postcapillary venules in both the hydronephrotic and the nonhydronephrotic kidneys. Glomeruli could only be regularly seen in the hydronephrotic kidney, but also in some normal kidneys. Capillary blood cell velocity was significantly higher in the hydronephrotic kidneys (0.67 +/- 0.03 mm/s) compared to the normal kidney (0.32 +/- 0.05 mm/s; P < 0.05), whereas capillary diameters were smaller (4.2 +/- 0.02 microm vs. 5.7 +/- 0.2 microm; P < 0.05). In addition, the hydronephrotic kidney showed a significantly lower density of perfused microvessels compared to the normal controls. Epiillumination intravital microscopy allows assessment of the cortical microcirculation in both the hydronephrotic and the nonhydronephrotic kidneys without surgical induction of hydronephrosis. The hydronephrotic kidney shows significant microcirculatory differences compared to normal kidneys that should be taken into account when using a hydronephrotic model for pharmacological testing.


Asunto(s)
Hidronefrosis/congénito , Hidronefrosis/fisiopatología , Riñón/irrigación sanguínea , Circulación Renal/fisiología , Animales , Adhesión Celular/fisiología , Colorantes Fluorescentes/metabolismo , Leucocitos/metabolismo , Microcirculación , Microscopía/métodos , Perfusión , Ratas
17.
Urol Int ; 67(1): 104-8, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11464132

RESUMEN

A clear cell adenocarcinoma of the urethra associated with so-called nephrogenic metaplasia occurring in a 57-year-old male patient is presented. Ten months following total urethrectomy, multiple pulmonary metastases had developed. The patient died 2.5 years after surgery. The possible histogenesis of clear cell adenocarcinoma of the lower urinary tract - reported to develop in the male urethra only in a very few cases - is reviewed briefly. We favor an origin from preexisting nephrogenic metaplasia as one of the possible histogenetic pathways.


Asunto(s)
Adenocarcinoma de Células Claras/patología , Uretra/patología , Neoplasias Uretrales/patología , Humanos , Masculino , Metaplasia , Persona de Mediana Edad
18.
J Urol ; 165(6 Pt 2): 2289-92, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11371964

RESUMEN

PURPOSE: Alterations caused by renal obstruction in developing kidneys are of particular interest in basic research of congenital obstructive uropathy. In rats nephrogenesis mainly occurs 7 to 10 days postnatally. Therefore, surgically induced neonatal ureteral obstruction in rats has been suggested to be analogous to congenital obstruction in the fetus. An attempt less prone to surgical artifacts and assessing even earlier developmental stages is to monitor the development of obstructed kidneys in rats with congenital obstructive uropathy. MATERIALS AND METHODS: Rats from an inbred strain with congenital renal obstruction in 70% of their littermates were observed. Morphologically, significant hydronephrosis was not detected before day 5 post partum and progressed with age. Unilateral obstructed kidneys were compared with contralateral kidneys and kidneys from healthy control animals at ages of 1, 5, 10, 18 and 32 days. A total of 72 renal units were investigated. The renal messenger RNA expression of renin and transforming growth factor-beta1 (TGF-beta1) was quantified by competitive quantitative reverse transcription polymerase chain reaction using a gene specific complementary RNA standard. RESULTS: In controls the gene expression of renin decreased from day 1 to day 18 and remained stable. TGF-beta1 expression increased during the first 10 days and then decreased again. Renin expression of the obstructed kidneys was reduced (p <0.05) on day 1, increased to a maximum versus controls (p <0.01) on day 10 and decreased to an unchanged elevated level (p <0.01) on days 18 and 32. Renin expression of the contralateral kidneys showed no significant alterations to control kidneys. Messenger RNA expression of TGF-beta1 of obstructed kidneys stayed decreased during the first 10 days (p <0.05), then increased excessively on day 18 (p <0.01) and slightly decreased on day 32. TGF-beta1 expression of the contralateral kidneys was parallel to controls on a slightly elevated level, increased on day 18 and returned to control level on day 32. CONCLUSIONS: Within the postpartum period of nephrogenesis gene expression of renin and TGF-beta1 was decreased in obstructed kidneys compared to controls. As the renin angiotensin system and TGF-beta1 have important functions in normal kidney development, these results suggest impaired nephrogenesis of congenital obstructed kidneys even before the onset of morphological signs of hydronephrosis. These features differ from surgical induced unilateral ureteral obstruction at birth and promise new insights into the pathophysiology of congenital obstructive uropathy.


Asunto(s)
Expresión Génica , Hidronefrosis/fisiopatología , Renina/genética , Factor de Crecimiento Transformador beta/metabolismo , Animales , Femenino , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas
19.
J Med Chem ; 44(8): 1158-76, 2001 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-11312916

RESUMEN

Antagonists of the platelet fibrinogen receptor (GP IIb/IIIa receptor) are expected to be a promising new class of antithrombotic agents. The binding of fibrinogen to the fibrinogen receptor depends on an Arg-Gly-Asp-Ser (RGDS) tetrapeptide recognition motif. Structural modifications of the RGDS lead have led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist 44 (S 1197). Compound 44 inhibited, in a dose dependent and reversible manner, human and dog platelet aggregation as well as 125I-fibrinogen binding to ADP-activated human gel filtered platelets and isolated GP IIb/IIIa with K(i) values of 9 nM and 0.17 nM, respectively. A pharmacophore mapping procedure with QXP and a 3D-QSAR analysis applying the GRID/GOLPE methodology yielded a stable, rather predictive model and revealed structural features which are important for binding. Hydrophobic substitutions both at the hydantoin nucleus and at the C-terminus increase the affinity toward the fibrinogen receptor. The crystalline ethyl ester prodrug 48 (HMR 1794) is an orally active antithrombotic agent which is a promising drug candidate for the treatment of thrombotic diseases in humans.


Asunto(s)
Hidantoínas/síntesis química , Imidazoles/síntesis química , Inhibidores de Agregación Plaquetaria/síntesis química , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Profármacos/síntesis química , Propionatos/síntesis química , Administración Oral , Animales , Plaquetas/metabolismo , Perros , Fibrinógeno/metabolismo , Humanos , Hidantoínas/química , Hidantoínas/farmacología , Imidazoles/química , Imidazoles/farmacología , Recién Nacido , Modelos Moleculares , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/farmacología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Profármacos/química , Profármacos/farmacología , Propionatos/química , Propionatos/farmacología , Relación Estructura-Actividad Cuantitativa , Estereoisomerismo
20.
Urol Res ; 28(2): 104-9, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10850632

RESUMEN

Partial obstruction of the upper urinary tract, a frequent challenge for the pediatric urologist, leads to renal damage, if deobstruction is delayed. Several but sometimes unsatisfactory animal models have been developed to study this phenomenon. Obstruction created by surgical manipulation lacks adequate correlation with a developing congenital obstruction. In some animals with congenital hydronephrosis, evidence of renal obstruction is absent. A study of the renal morphology of rats with hereditary unilateral hydronephrosis has exhibited clear evidence of renal obstruction distinguishable from renal dilatation. The renal mRNA expression of renin and transforming-growth factor-beta1 (TGF-beta1) was measured by a semiquantitative RT-PCR technique. In hydronephrotic kidneys, a marked loss of parenchyma, atrophy and dilation of tubuli and collecting ducts and interstitial fibrosis was observed. The mRNA expression of renin was increased significantly in comparison to controls, whereas the contralateral kidneys showed renin activity below control levels. TGF-beta1 expression was markedly increased in hydronephrotic kidneys, whereas contralateral kidneys did not differ significantly from control values. These data suggest the presence of renal obstruction and not only renal dilatation in these rats with congenital hydronephrosis. This colony seems to be a representative animal model to study congenital renal obstruction even in the fetal period without the need of surgical manipulation.


Asunto(s)
Hidronefrosis/patología , Obstrucción Ureteral/patología , Actinas/genética , Animales , Cartilla de ADN , Fibrosis , Expresión Génica/fisiología , Hidronefrosis/congénito , Hidronefrosis/genética , Riñón/patología , Riñón/fisiología , ARN Mensajero/análisis , Ratas , Sistema Renina-Angiotensina/genética , Factor de Crecimiento Transformador beta/genética , Obstrucción Ureteral/genética
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