Protective effects of Tadalafil and darbepoetin against ischemia - reperfusion injury in a rat testicular torsion model

ABSTRACT Objectives: To evaluate protective effects of darbepoetin and tadalafil against ischemia-reperfusion injury in ipsilateral and contralateral testicle. Materials and Methods: Thirty 3-month-old adult male Wistar-Albino rats were randomly divided into 5 groups (A-E). Sham operation was performed in the first group. In Group B, rats did not received any medication after creating 720 degrees torsion of the left testis. The rats in Group C, D and E received darbepoetin, tadalafil, and darbepoetin/tadalafil combination 30 minutes after creating 720 degrees torsion of the left testis, respectively. The testes of rats in these three groups were detorsioned at 90 minutes after drug administration. Both testes were removed at 30 minutes after detorsion. Results: There were significant differences between the groups in terms of the degree of histopathological damage, Johnsen score, fibrosis score and caspase-3 immunoreactivity in the torsioned testes (p: 0.000). The results for each parameter in the left testes were significantly better in the darbepoetin / tadalafil combination group. Similarly, there were also significant differences in the contralateral testes (p: 0.000). Conclusion: The active substances darbepoetin and tadalafil that were used as a combination had protective effects on both testes and produced out better results in preserving testicular histology. Especially in cases where it is not possible to rescue the torsioned testis, this result was more noticeable in the contralateral testis.

Effectiveness of darbepoetin alfa in multiple myeloma patients receiving chemotherapy including novel agents

BACKGROUND: The aim of this study was to evaluate the effects of darbepoetin alfa (DA) on hemoglobin (Hb) concentration and the need for transfusions in multiple myeloma (MM) patients receiving chemotherapy with novel agents. METHODS: Of 251 patients with MM who received DA therapy for at least 4 weeks, 142 who did not receive RBC transfusion during 4 weeks after DA initiation and started DA therapy at baseline Hb <10.0 g/dL were analyzed. RESULTS: After 4 weeks of DA therapy, 80 (60.6%) of 132 patients with evaluable data had Hb that increased ≥1.0 g/dL from baseline, while 50 (37.9%) had Hb that increased ≥2.0 g/dL from baseline. Pretreatment Hb level did not correlate with the proportion of patients with increased Hb. The median duration of DA therapy was 9.0 weeks. At the end of DA therapy, of 135 patients with evaluable data, 86 (60.6%) had Hb that increased ≥1.0 g/dL from baseline, while 67 (47.2%) had Hb that increased ≥2.0 g/dL from baseline. Stage III disease according to the International Staging System and absence of myeloma bone disease at diagnosis were independent predictors of higher Hb response during early DA therapy. CONCLUSION: We demonstrated the efficacy of DA therapy in a homogeneous group of MM patients receiving chemotherapy. DA therapy significantly increased Hb concentration, regardless of baseline Hb level.

Probiotic dietary supplementation in a dog with chronic kidney disease / 동물의과학연구지

A 7-year-old spayed female English Cocker Spaniel dog presented with polyuria (PU), polydipsia (PD), intermittent vomiting, and weight loss. Physical examination revealed pale, tacky mucous membranes and severe emaciation. Hematological and biochemical examinations revealed moderate normocytic normochromic non-regenerative anemia and moderate azotemia. Abdominal ultrasonography demonstrated bilaterally small lumpy-bumpy kidneys with hyperechoic parenchyma as well as loss of renal corticomedullary junction. Based on clinical history and examinations, the dog was diagnosed with chronic kidney disease (CKD). The dog was treated with supportive care including fluid therapy, phosphate-binding agent, and histamine H2-receptor antagonist. Darbepoetin Alfa was administered to control renal secondary non-regenerative anemia. Prescribed diet with low-protein and low-phosphorus was fed to alleviate CKD signs. Further, dietary probiotics were supplemented. This case demonstrates that oral probiotic supplementation helped reduce blood urea-nitrogen (BUN) levels. This case indicates that dietary probiotics can be a potential alternative therapeutic agent for management of renal failure.

Hemoglobin Variability Associated with Different Erythropoiesis Stimulating Agents in Hemodialysis Patients / 대한신장학회지

PURPOSE: This study was undertaken to examine whether differences exist in the hemoglobin variability according to the types of erythropoiesis stimulating agent (ESA) in hemodialysis (HD) patients. METHODS: Clinical data were retrospectively analyzed from 72 patients on maintenance hemodialysis who were using darbepoetin alfa (n=27), epoetin beta (n=27), and epoetin alpha (n=18). As parameters of hemoglobin variability, hemoglobin cycling, the variance of hemoglobin and the SD/mean of hemoglobin were analyzed. Hemoglobin cycling was defined as the presence of cycles with an amplitude >1.5 g/dL and lasting more than 2 months. RESULTS: Hemoglobin cycling was present in 53 (73.6%) out of 72 HD patients. Hemoglobin cycling in patients receiving darbepoetin alfa had greater frequency (1.63+/-0.93 vs. 1.00+/-0.88 times/year, p<0.05), amplitude (2.88+/-1.48 vs. 1.88+/-1.60 g/dL, p<0.05), and velocity (1.21+/-0.74 vs. 0.73+/-0.66 g/dL/month, p<0.05) than that in patients receiving epoetin beta. The variance of hemoglobin in patients receiving epoetin beta (0.79+/-0.53 g/dL) was smaller than that in patients receiving darbepoetin alfa (1.29+/-0.70 g/dL, p<0.05) and epoetin alfa (1.08+/-0.52 g/dL, p<0.05). Also, the ratio of SD/mean of hemoglobin in patients receiving epoetin beta (8.20+/-2.59%) was lower than that in patients receiving darbepoetin alfa (10.81+/-2.10%, p<0.05) and epoetin alfa (10.30+/-2.10%, p<0.05). CONCLUSION: Hemoglobin variability is differential according to various ESAs, and it may be less with epoetin beta compared with darbepoetin alpha and epoetin alpha.

Efficacy of Darbepoetin alfa in Anemia Developed during Chemotherapy for Lung Cancer / 결핵및호흡기질환

BACKGROUND: Anemia is quite common in lung cancer patients and known to decrease the quality of life. Darbepoetin alfa is an erythropoiesis-stimulating protein approved for administration to cancer patients. This study examined the efficacy and safety of darbepoetin alfa in lung cancer patients with a hemoglobin concentration 10 g/dl. The efficacy and safety were measured by comparing the hemoglobin concentration and assessing the adverse events. RESULTS: After chemotherapy, the hemoglobin concentration decreased to 9.03+/-0.64 g/dl. With the darbepoetin alfa treatment, the hemoglobin concentration increased to 10.09+/-1.17 g/dl after 4 weeks reaching a peak hemoglobin concentration of 10.45+/-1.18 g/dl. The changes in hemoglobin after 4 and 8 weeks with treatment were 1.08+/-1.24 g/dl and 1.38+/-1.59 g/dl (p<0.01). At least a 1 g/dl or more increase in hemoglobin was observed in 62.4% of patients. There were no serious adverse effects except for some mild reactions. CONCLUSION: Darbepoetin alfa administered to lung cancer patients appears to be an effective, well-tolerated treatment for chemotherapy induced anemia.

Comparison of Erythropoietic Effect between Epoetin-alpha and Darbepoetin-alpha in Hemodialysis Patients: A Randomized Crossover Study / 대한신장학회지

PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of 11.0 g/dL, we stopped ESA. When Hb level decreased to 30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.

Randomized, Controlled Trial of Darbepoetin Alfa for the Treatment of Renal Anemia in Hemodialysis Patients / 대한신장학회잡지

BACKGROUND: Darbepoetin alfa is a new erythropoietic agent with a three fold longer terminal half-life than recombinant human erythropoietin (r- HuEPO). The aim of this randomized, open-label study is to determine whether darbepoetin alfa is as effective as r-HuEPO for the treatment of anemia in hemodialysis patients when administered at a reduced dosing frequency. METHODS: A total 74 Korean hemodialysis patients receiving r-HuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized to continue r-HuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dosing frequency. Patients receiving r-HuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving r-HuEPO two or three times weekly changed to once-weekly darbepoetin alfa. The initial dose of darbepoetin alfa was based on the r-HuEPO dose at the time of entry into the study, using a formula equating the peptide mass of the two molecules (200 IU r-HuEPO=1 microgram darbepoetin alfa). The doses of r-HuEPO and darbepoetin alfa were titrated to maintain hemoglobin concentrations within -1.0 to +1.5 g/dL of patients' baseline values and within a range of 8.0 to 13.0 g/ dL for up to 20 weeks (16-week dose-titration period followed by a 4-week evaluation period). The primary end point was change in hemoglobin level between baseline and the evaluation period. RESULTS: The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (-0.03+/-0.19 g/dL) and r-HuEPO (0.27+/-0.20 g/dL) groups, and the difference between the two treatments was -0.30 g/dL (95% CI, -0.84 to 0.23). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. The safety profiles of darbepoetin alfa and r-HuEPO were similar. CONCLUSION: This study suggests that darbepoetin alfa maintains hemoglobin as effectively as r- HuEPO, but with reduced dose frequency.