Failure of isolated kidney transplantation in a pediatric patient with primary hyperoxaluria type 2

PH type 2 is caused by decreased activity of GRHPR enzyme that eventually leads to ESRD and systemic oxalosis. Here, we describe an Iranian pediatric patient with PH2 and early ESRD development who received recommended treatment by undergoing isolated kidney transplantation. Diagnosis criteria included a history of reoccurring calcium oxalate renal stones and elevated oxalate levels combined with liver biopsy and decreased enzymatic activity at age five. ESRD prompted transplantation and was performed at age nine. On Day 12 post‐op, his serum creatinine level increased. A graft biopsy showed calcium oxalate crystal deposits in renal tubes with no evidence of acute rejection, which resolved with intensive hydration and administration of a potassium citrate solution. Subsequent biopsies confirmed results found in first biopsy. Despite the immunosuppressive therapy, his serum creatinine level increased again after 11 months. Renal tubular obstruction then led to graft nephrectomy. Pathological analysis of tissue confirmed findings of past biopsies. This was a very rare case of early ESRD in PH2 resulting in a failed isolated kidney transplant. As the GRHPR enzyme is predominantly expressed in liver, we suggest a combined liver‐kidney transplant may be beneficial in patients with PH2.     

Tropisetron ameliorates early diabetic nephropathy in streptozotocin‐induced diabetic rats

It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti‐inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin‐induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor‐α were also determined. Streptozotocin‐treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor‐α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor‐α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti‐oxidative and anti‐inflammatory mechanisms that appear to be independent of the 5‐HT₃ receptor.     

Omega-3 Poly-Unsaturated Fatty Acids for the Prevention of Severe Neutropenic Enterocolitis in Patients with Acute Myeloid Leukemia

Neutropenic enterocolitis is a potentially fatal complication of myeloablative chemotherapy in patients with acute myeloid leukemia. Omega-3 polyunsaturated fatty acids (PUFA) are precursors of potent anti-inflammatory prostaglandins. Our aim was to explore the safety and effectiveness of omega-3 PUFA added to parenteral nutrition in protecting leukemia patients from severe enterocolitis. Fourteen patients with acute myeloid leukemia who received omega-3 PUFA in a Phase II trial were compared with 66 consecutive control patients not getting this intervention. We performed crude and adjusted comparisons, using inverse probability of treatment weighting for adjusted analysis, and blind outcome assessment to minimize assessor bias. Primary outcome was severe enterocolitis (≥Grade 3). The crude odds ratio of Grade 3 colitis or higher was 1.36 (95% CI 0.37 to 4.96, P = 0.64), and the adjusted odds ratio was 0.79 (95% CI 0.35 to 1.78, P = 0.57). There was little evidence to suggest differences between groups in serious adverse events and overall mortality. Our results provide little evidence that addition of omega-3 PUFA is beneficial in this condition. Routine treatment with omega-3 PUFA is currently not warranted.     

CK2 phosphorylates the angiotensin-converting enzyme and regulates its retention in the endothelial cell plasma membrane

Soluble angiotensin-converting enzyme (ACE) is derived from the membrane-bound form by proteolytic cleavage of its C-terminal domain. Because intracellular events might be involved in the regulation of the cleavage process, we determined whether the cytoplasmic tail of ACE is phosphorylated and whether this process regulates secretion. Immunoprecipitation of ACE (180 kDa) from (32)P-labeled endothelial cells revealed that ACE is phosphorylated. Phosphorylation was not observed in endothelial cells overexpressing a mutant form of ACE (ACEDeltaS, all five cytoplasmic serine residues replaced by alanine). CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation. In ACE-overexpressing endothelial cells, ACE was mostly localized to the plasma membrane. However, no ACE was detected in the plasma membrane of ACEDeltaS-overexpressing cells, although a precursor ACE (170 kDa) was prominent in the endoplasmic reticulum and the cell supernatant contained substantial amounts of the soluble protein (175 kDa). A correlation between ACE-phosphorylation and secretion was confirmed in endothelial cells treated with the CK2-inhibitor, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which time-dependently decreased the phosphorylation of ACE and increased its shedding. These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels.     

Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

AIM: To analyze the phenotype and function of dendritic cells (DC) from patients with hepatocellular carcinoma (HCC) in order to understand their role in this disease. METHODS: Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dI:dC was tested. RESULTS: Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion. CONCLUSION: Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.     

A novel n-type CdS nanorods/p-type LaFeO3 heterojunction nanocomposite with enhanced visible-light photocatalytic performance

In this work, a novel n-type CdS nanorods/p-type LaFeO₃ (CdS NRs/LFO) nanocomposite was prepared, for the first time, via a facile solvothermal method. The as-prepared n-CdS NRs/p-LFO nanocomposite was characterized by using powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDX), UV-visible diffuse reflection spectroscopy (DRS), vibrating sample magnetometry (VSM), photoluminescence (PL) spectroscopy, and Brunauer–Emmett–Teller (BET) surface area analysis. All data revealed the attachment of the LFO nanoparticle on the surface of CdS NRs. This novel nanocomposite was applied as a novel visible light photocatalyst for the degradation of methylene blue (MB), rhodamine B (RhB) and methyl orange (MO) dyes under visible-light irradiation. Under optimized conditions, the degradation efficiency was 97.5% for MB, 80% for RhB and 85% for MO in the presence of H₂O₂ and over CdS NRs/LFO nanocomposite. The photocatalytic activity of CdS NRs/LFO was almost 16 and 8 times as high as those of the pristine CdS NRs and pure LFO, respectively. The photocatalytic activity was enhanced mainly due to the high efficiency in separation of electron–hole pairs induced by the remarkable synergistic effects of CdS and LFO semiconductors. After the photocatalytic reaction, the nanocomposite can be easily separated from the reaction solution and reused several times without loss of its photocatalytic activity. Trapping experiments indicated that ·OH radicals were the main reactive species for dye degradation in the present photocatalytic system. On the basis of the experimental results and estimated energy band positions, the mechanism for the enhanced photocatalytic activity was proposed.

A novel n–p CdS nanorods/LaFeO₃ (CdS NRs/LFO) heterojunction nanocomposite was prepared via a solvothermal route and applied as a visible-light photocatalyst for enhanced degradation of organic dye pollutants.     

Kaposi’s sarcoma following living donor kidney transplantation: review of 7,939 recipients

Introduction  Kaposi’s sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. Methods  Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. Results  Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1–180) months. KS occurred more often in older age when compared to patients without KS (49 ± 12 vs. 38 ± 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). Conclusion  The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.