Randomized Study of Darbepoetin Alfa and Recombinant Human Erythropoietin for Treatment of Renal Anemia in Chronic Renal Failure Patients Receiving Peritoneal Dialysis

Background/PurposeDarbepoetin alfa can be administered less frequently than recombinant human erythropoietin (r-HuEPO) for the treatment of anemia in chronic renal failure (CRF) patients. We aimed to confirm that darbepoetin alfa at a reduced dosing schedule can safely maintain a target hemoglobin level in CRF patients undergoing peritoneal dialysis.MethodsForty-five PD patients receiving r-HuEPO were randomized in a 1:1 ratio to continue r-HuEPO or to change to darbepoetin alfa (open-label). Patients were maintained within a target range of hemoglobin for 5.5 months by adjusting the dose and then the frequency of darbepoetin alfa and r-HuEPO over the initial 4 months. The evaluation period was the final 1.5 months. A total of 37 patients completed the study.ResultsDuring the evaluation period, the hemoglobin of the darbepoetin alfa group was higher than that in the baseline period (10.46 ± 0.22 g/dL vs. 9.98 ± 0.18 g/dL, p < 0.05). Hemoglobin remained similar in the r-HuEPO group. The average dose in the darbepoetin alfa group was 93.0 μg/month, while the average dose in the r-HuEPO group was 18,339.9 units/month. The dosing frequency was less in the darbepoetin alfa group (3.9 times/month vs. 9.2 times/month). We divided the darbepoetin alfa group into low-dose (< 70 μg/month) and high-dose (≥ 70 μg/month) subgroups. The body weight in the high-dose group was higher than that in the low-dose group (66 ± 11 kg vs. 52 ± 4.4 kg, p < 0.01).ConclusionBoth darbepoetin alfa and r-HuEPO safely maintain hemoglobin levels within the target range in peritoneal dialysis patients

A 52-Year-Old Woman with a Palpable Abdominal Mass

A 52-year-old woman presented with a history of diabetes mellitus under medical treatment and a surgical history of a cesarean section 20 years ago. The patient was referred to our emergency department because of a 2-week hypermenorrhea and unspecific abdominal pain without nausea and vomiting, fever, or other symptoms. She did not complain of weight loss

A 5-Month-Old Infant with Right Scrotum Swelling

Case presentation:A five-month-old male infant (gestational age 28 weeks, birthweight 1020 gm) with posthemorrhagic hydrocephalus subsequent to prematurity had a left sided ventriculoperitoneal shunt 3 months after birth. Frontal radiography of the chest and abdomen check-up after operation are shown in figure 1. He was referred to our emergency department with a history of right scrotal swelling for several days. Physical examination, he appeared malnourished. He was afebrile. The right scrotum was found to be distended. Bilateral testicles were palpable on both sides. There were no features of shunt malfunction. A complete blood cell count showed the following: leukocyte count, 7900/mm3; segmented neutrophils, 65%; hemoglobin level of 9.3 mg/dL; hematocrit, 25.9%; and platelet, 190000/uL. Other laboratory studies included: glucose, 92 mg/dL; serum urea nitrogen, 10 mg/dL; serum creatinine, 0.2 mg/dL; sodium, 140 mEq/L; potassium, 3.9 mEq/L; C-reactive protein, 2.9mg/L; and prothrombin time with an international normalized ratio of 1.2. His abdomen x-ray is shown in figure 2. 

A 33-year-old Man with Abdominal Pain

A 33-year-old man presented to the emergency department ED) with complaint of 2-day history of abdominal pain. His pain developed with gradual onset prominently in epigastric area after eating dried mushrooms. The pain was diffuse, persistent, radiating to the back and aggravated by meal. He had been tolerating only liquids and had complaints of nausea and vomiting. He had no history of diabetes mellitus, hypertension, alcohol consumption, malignancy, or prior surgery. On arrival his blood pressure was 128/72 mmHg, with a heart rate of 101 beats/minute and a respiratory rate of 20 breaths/minute. He was afebrile. Physical examination revealed diffuse abdominal distention, hyper-pitched bowel sounds, and tenderness more marked over the umbilicus with no guarding or rebound tenderness. A complete blood cell count showed the following: leukocyte count 12600 /mm3; segmented neutrophils 90%; hemoglobin level of 14 mg/dl; hematocrit 30%; and platelet 420000/µL. Other laboratory studies included: glucose 101 mg/dL; serum urea nitrogen 45 mg/dL; serum creatinine 2.0 mg/dL; sodium 148 mEq/L; potassium 3.1 mEq/L; serum glutamic oxaloacetic transaminase (SGOT) 38 U/L and lipase 30 U/L. Figure 1 shows patient’s plain upright abdominal X-ray as well as coronal and axial cuts of abdominal CT scan

Cell-based analysis of Chikungunya virus E1 protein in membrane fusion

<p>Abstract</p> <p>Background</p> <p>Chikungunya fever is a pandemic disease caused by the mosquito-borne Chikungunya virus (CHIKV). E1 glycoprotein mediation of viral membrane fusion during CHIKV infection is a crucial step in the release of viral genome into the host cytoplasm for replication. How the E1 structure determines membrane fusion and whether other CHIKV structural proteins participate in E1 fusion activity remain largely unexplored.</p> <p>Methods</p> <p>A bicistronic baculovirus expression system to produce recombinant baculoviruses for cell-based assay was used. Sf21 insect cells infected by recombinant baculoviruses bearing wild type or single-amino-acid substitution of CHIKV E1 and EGFP (enhanced green fluorescence protein) were employed to investigate the roles of four E1 amino acid residues (G91, V178, A226, and H230) in membrane fusion activity.</p> <p>Results</p> <p>Western blot analysis revealed that the E1 expression level and surface features in wild type and mutant substituted cells were similar. However, cell fusion assay found that those cells infected by CHIKV E1-H230A mutant baculovirus showed little fusion activity, and those bearing CHIKV E1-G91D mutant completely lost the ability to induce cell-cell fusion. Cells infected by recombinant baculoviruses of CHIKV E1-A226V and E1-V178A mutants exhibited the same membrane fusion capability as wild type. Although the E1 expression level of cells bearing monomeric-E1-based constructs (expressing E1 only) was greater than that of cells bearing 26S-based constructs (expressing all structural proteins), the sizes of syncytial cells induced by infection of baculoviruses containing 26S-based constructs were larger than those from infections having monomeric-E1 constructs, suggesting that other viral structure proteins participate or regulate E1 fusion activity. Furthermore, membrane fusion in cells infected by baculovirus bearing the A226V mutation constructs exhibited increased cholesterol-dependences and lower pH thresholds. Cells bearing the V178A mutation exhibited a slight decrease in cholesterol-dependence and a higher-pH threshold for fusion.</p> <p>Conclusions</p> <p>Cells expressing amino acid substitutions of conserved protein E1 residues of E1-G91 and E1-H230 lost most of the CHIKV E1-mediated membrane fusion activity. Cells expressing mutations of less-conserved amino acids, E1-V178A and E1-A226V, retained membrane fusion activity to levels similar to those expressing wild type E1, but their fusion properties of pH threshold and cholesterol dependence were slightly altered.</p

Orderly arranged NLO materials on exfoliated layeredtemplates based on dendrons with alternating moietiesat the periphery†

Nonlinear optical dendrons with alternating terminal groups of the stearyl group (C18) and chromophorewere prepared through a convergent approach. These chromophore-containing dendrons were used asthe intercalating agents for montmorillonite via an ion-exchange process. An orderly exfoliatedmorphology is obtained by mixing the dendritic structure intercalated layered silicates with a polyimide.As a result, optical nonlinearity, i.e. the Pockels effect was observed for these nanocomposites withoutresorting to the poling process. EO coefficients of 9–22 pm V 1 were achieved despite that relativelylow NLO densities were present in the nanocomposites, particularly for the samples comprising thedendrons with alternating moieties. In addition, the hedging effects of the stearyl group on the selfalignmentbehavior, electro-optical (EO) coefficient and temporal stability of the dendron-intercalatedmontmorillonite/polyimide nanocomposites were also investigated

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45ml/min per 1.73m2. AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 3.3) than patients with AKI but without CKD. The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge

Safety Issues of Long-Term Glucose Load in Patients on Peritoneal Dialysis—A 7-Year Cohort Study

BACKGROUND: Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. METHODS: We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates. RESULTS: We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. CONCLUSIONS: Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients