Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats.

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

Role of recombinant human erythropoietin against mitomycin C-induced cardiac, hepatic and renal dysfunction in Wistar rats.

Mitomycin C (MMC) is one of the most effective chemotherapeutic drugs. However, the dose of MMC is greatly limited by its toxicity in normal tissues. Recombinant human erythropoietin (rhEPO), an erythropoietic hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against MMC-induced heart, liver, and renal dysfunction. Adult male Wistar rats were divided into six groups (with six animals each), namely control, rhEPO alone group, MMC alone group, and rhEPO + MMC group (pre-, co-, and posttreatment conditions). The results showed that MMC induced a marked cardiac, renal, and liver failure characterized by a significant decrease in body weight, organs weight, and organs ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and conjugated and total bilirubin levels in serum. Histological examination showed that MMC caused liver alterations. rhEPO treatment restored body weight, organs weight, and organs ratio as well as serum biochemical parameters and histological damage caused by MMC exposure.

The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats.

Cisplatin (Cisp) is one of the most effective chemotherapeutic drugs. However, the dose of Cisp is greatly limited by its toxicity. Recombinant human erythropoietin (rhEPO), a hormone that regulates hematopoiesis, has also been shown to exert tissue-protective effects. The purpose of this study was to explore the protective effect of rhEPO against Cisp-induced renal and liver dysfunctions. Adult male Wistar rats were divided into six groups of six each: control, rhEPO-alone group, Cisp-alone group and rhEPO + Cisp group (pretreatment, cotreatment and posttreatment conditions). Our results showed that Cisp-induced a marked renal and liver failure characterized by a significant decrease in body weight, organ weight and organ ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, G-glutamyl transferase, alkaline phosphatase, bilirubin conjugated and bilirubin total levels in serum. Histological examination showed that Cisp caused kidney alterations. rhEPO treatments restored body weight, organ weight and organ ratio as well as serum biochemical parameters changed due to Cisp exposure.

[Postnatal investigation and outcome of isolated fetal renal pelvis dilatation]. / Exploration post-natale et devenir des pyélectasies foetales isolées.

UNLABELLED: The purpose of this study was to evaluate the prognosis of fetal renal pelvis dilatation in relation to the degree of prenatal dilatation and the postnatal ultrasonography assessment. Based on these results, an algorithm is proposed for the choice of postnatal investigations and follow-up in children with fetal renal pelvis dilatation. MATERIAL AND METHODS: The study was conducted prospectively among 10,677 newborns in Avignon over a nearly 5-year period. Infants with an anteroposterior pelvic diameter (APPD) 5mm or greater in the second trimester were enrolled with a threshold for the normal renal pelvis dimensions increasing with advancing gestation. Prenatal ultrasound was correlated with the results of postnatal investigation and frequency of surgical uropathy was established. RESULTS: Pyelectasis was found in 1% of pregnancies and among 100 infants whose cases were followed, 23 (23%) had uropathies (seven isolated pelviureteric junction obstruction [PUJ], nine isolated vesicoureteral reflux [VUR], three VUR+PUJ, two duplicity, one obstructive megaureter, and one multicystic dysplastic kidney). The largest group of fetuses (66/100) had minor fetal pyelectasis of less than 10mm: in this group, 90% of the infants had no uropathy and there was no surgery. Six of 34 (17%) in the moderate (APPD> or =10 and<15mm) and severe (APPD> or =15mm) fetal pyelectasis groups required surgery, especially those with progressive PUJ obstructions. When postnatal ultrasound was normal in 64 infants (64%), there were only three mild or moderate (grades I-III), asymptomatic, and spontaneously resolving VUR. When pyelectasis was isolated and 10mm< or =APPD<15mm, cystourethrography was normal in 70% of the cases and only four cases of spontaneously resolving VUR were found. Among 23 infants with uropathies, six of 23 required surgery (26%), especially PUJ stenosis (5/6) with APPD greater than 15mm. In the total population of fetal pyelectasis, postnatal ultrasound predicted renal abnormalities with a sensitivity of 87% and a negative predictive value of 95%. CONCLUSION: Normal neonatal ultrasound rarely coexists with significant abnormal findings and there seems to be no need for additional investigations when postnatal echography is normal. Cystourethrography can be delayed when pyelectasis is isolated with 10mm< or =APPD<15mm. Isolated and uninfected cases of VUR do not require surgery and all mild and moderate cases of VUR spontaneously resolved. All PUJ stenoses with APPD greater than 15mm required surgery.

Radioimmunoassay of bovine placental lactogen using recombinant and native preparations: determination of fetal concentrations across gestation.

Concentrations of bovine placental lactogen (bPL) were determined in fetal plasma samples by twelve double-antibody competitive radioimmunoassay systems (RIA I-XII) based on either recombinant bPL (non-glycosylated) or native bPL (glycosylated). Both preparations were used as standard and tracer, and for primary antisera production. The minimum detection limit measured by these RIA varied from 0.02 to 0.6 ng bPL mL(-1). The coefficients of correlation of different bPL RIA systems were up to 90% (P < 0.0001) when each RIA was tested against the average values of all twelve RIA systems. All developed RIA were used to investigate the incidence of different bPL isoforms in bovine fetal serum samples (n = 71). Fetal concentrations ranged from 11.8 to 35.7 ng mL(-1) at the third month and from 1.1 to 13.5 ng mL(-1) at the ninth month of gestation. They tended to decrease with advancing gestation. In general, those RIA systems that used recombinant bPL as the standard measured higher values than those using the native bPL preparation. These differences decreased toward the end of gestation (P < 0.05), suggesting a lower rate of glycosylation. Our results provide evidence of different glycosylated isoforms of bPL in fetal serum at different gestation periods.

Retrospective study of 99 cases of bone fractures in cattle treated by external coaptation or confinement.

Between 2000 and 2003, 99 cattle with limb fractures were treated. Over 50 per cent were tibial fractures, with the femur and os calcis being the second and third most frequently affected bones. Eight of the cattle were slaughtered because of their poor prognosis, 10 were treated by stall confinement, 76 were treated by external coaptation with a Thomas splint-cast combination and three were treated with a simple or reinforced half limb cast; these 79 cattle were usually discharged immediately. One calf was treated with internal fixation, and another by amputation. Follow-up information was obtained by telephone, and the treatments were classified as either completely successful (return to previous production level), partially successful (return to lower production level) or failure. Forty (52.6 per cent) of the cattle treated with the Thomas splint-cast combination were classified as a complete success and 14 (18.4 per cent) as a partial success; the treatment failed in 19 of the cattle and three were lost to follow-up. The animals' bodyweight, age and sex, and whether the fracture was open or closed, had no significant influence on the outcome. Among the 10 cattle treated for proximal fractures by stall confinement, there were five survivors, four non-survivors and one was lost to follow-up.

Viability of cloned bovine embryos after one or two cycles of nuclear transfer and in vitro culture.

We described an exclusively in vitro procedure for cloning and recloning bovine embryos. Embryos obtained by IVM/IVF/IVC developed to the morula stage were used as blastomere donors in cunjunction with IVM recipient oocytes. Reconstructed embryos were developed in vitro in co-culture using bovine oviductal epithelial cells. The resulting morulae were used as donors for recloning under the same experimental conditions. No significant difference was observed between cloning and recloning in terms of development (rates of blastocysts: 12.9 versus 14.9%), in the number of nuclei per blastocyst (63.8 versus 49.1), or in pregnancy rates (35.7 versus 33.3%). The high variability observed between replicates and the correlation between results in first and second cycle nuclear transfer may suggest an inherant potential of individual donor embryos to support development by cloning.

Some factors affecting successful vitrification of mouse blastocysts.

The effects of temperature and exposure time to vitrification solutions on In vitro survival of mouse blastocysts were investigated. Blastocysts were first exposed for 10 min to vitrification Solution 1 (VS1) containing 10% glycerol-20% 1,2 propanediol in phosphate buffered saline (PBS), then to vitrification Solution 2 (VS2) with 25 % glycerol-25% 1,2 propanediol for various periods either at room temperature or at 4 degrees C. At room temperature survival dropped quickly, while at 4 degrees C an increase in survival was observed. It is concluded that the viability of mouse blastocyts after vitrification is dependent on the temperature and duration of equilibration in vitrification solutions.