Abdominal catheter-induced intussusception following renal transplantation in two pediatric recipients: 2 cases report and literature review.

Background: Intussusception is a frequent abdominal emergency in the pediatric population when the proximal bowel invaginates into the distal bowel. However, catheter-induced intussusception has not previously been described in pediatric renal transplant recipients, and the risk factors need to be investigated. Case Description: We report 2 cases of post-transplant intussusception which were caused by abdominal catheters. Case 1 experienced ileocolonic intussusception 3 months after renal transplantation and presented with intermittent abdominal pain; the intussusception was successfully managed using air enema. However, this child experienced a total of 3 episodes of intussusception within 4 days, which discontinued only after removal of the peritoneal dialysis catheter. No further intussusception recurrence was observed and the patient's intermittent pain disappeared during the follow-up. Case 2 developed ileocolonic intussusception 2 days after renal transplantation and presented currant jelly stools. The intussusception was completely irreducible until the intraperitoneal drainage catheter was eliminated; the patient discharged normal feces during the following days. A search in the databases of PubMed, Web of Science, and Embase yielded 8 similar cases. Our 2 cases had a younger age at disease onset than those retrieved in the search, and abdominal catheter was revealed as a lead point. Possible leading points of the 8 previously reported cases included post-transplant lymphoproliferative disorder (PTLD), acute appendicitis, tuberculosis, lymphocele, and firm adhesions. We noted that our cases were managed successfully with nonoperative treatment, whereas the 8 reported cases underwent surgical intervention. All of the 10 cases of intussusception occurred after renal transplantation and showed that intussusception had been induced by a lead point. Conclusions: Our 2 cases implied that abdominal catheter could be a lead point to induce intussusception, especially in pediatric recipients with abdominal disorder. This experience may be applicable to other surgeries involving indwelling abdominal catheters in children. Health practitioners should consider this pathologic lead point and avoid serious consequences when intussusception occurs.

Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products.

BACKGROUND: As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for various types of solid tumors. Unfortunately, clinical application of this drug results in severe side effects of cardiotoxicity. PURPOSE: We aim to review the research focused on elimination or reduction of DOX cardiotoxicity without affecting its anticancer efficacy by natural products. METHODS: This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect. The literature mainly focusing on natural products and herb extracts with therapeutic efficacies against experimental models both in vitro and in vivo was identified. RESULTS: Current evidence revealed that multiple molecules and signaling pathways, such as oxidative stress, iron metabolism, and inflammation, are associated with DOX-induced cardiotoxicity. Based on these knowledge, various strategies were proposed, and thousands of compounds were screened. A number of natural products and herb extracts demonstrated potency in limiting DOX cardiotoxicity toward cultured cells and experimental animal models. CONCLUSIONS: Though a panel of natural products and herb extracts demonstrate protective effects on DOX-induced cardiotoxicity in cells and animal models, their therapeutic potentials for clinical needs further investigation.

Wuzhi Tablet (Schisandra sphenanthera Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study.

Tacrolimus is a potent but expensive first-line immunosuppressant, thus solutions to reduce tacrolimus consumption while maintain therapeutic level are in urgent need. A two-phase prospective study was conducted to assess the efficacy of an ethanolic extraction preparation of Schisandra sphenanthera (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers (CYP3A5*1 allele carriers, CYP3A5 expressers). A total of 12 patients were included in the Part I study. After co-administration of Wuzhi tablet, the average individual increment (%) in dose-adjusted C0, Cmax and AUC0-12 hour of tacrolimus were 198.8% (95% CI 149.2, 248.3), 111.0% (95% CI 63.4, 158.6) and 126.1% (95% CI 89.4, 162.8), respectively (P < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) (P < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by CYP3A5 genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement (P < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C0 after initial dose (P < 0.01) and fewer dose changes (P < 0.01) was found in the study group. Moreover, no significant differences in acute rejection rate and serum creatinine levels were observed between two groups. Our results show that CYP3A5 genotype plus Wuzhi tablet co-administration guided tacrolimus dosing is a promising therapy for CYP3A5 expressers in the early post-transplant stage, while further study with a larger sample size is required to prove these findings.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings.

This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1ß, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.

Effect and safety of Tripterygium Hypoglaucum (Lévl.) hutch in treating proteinuria of kidney transplant recipients.

OBJECTIVE: To investigate the therapeutic and adverse effects of Tripterygium hypoglaucum (Lévl.) Hutch (THH) in treating proteinuria of renal transplant recipients. METHODS: Thirty patients with proteinuria greater than 1 g/24 h were enrolled to be treated with one tablet preparation of THH extract (360 mg, 3 times daily, equivalent to triptolide 30 µg/d) for 6 months. The proteinuria, serum creatinine, sex hormones, semen analysis and erectile function in male were determined at entry, 3 and 6 months. Incidence of adverse events was evaluated. RESULTS: THH treatment significantly improved proteinuria (from 2.52±1.87 g/d at baseline to 1.11±0.96 g/d at 3 months, and to 1.04±1.09 g/d at 6 months). No significant changes were observed in serum creatinine, liver enzymes or complete blood count. In female (15 cases), THH treatment induced a significant increase in follicle stimulating hormone and luteinizing hormone levels, and a significant decrease in estradiol and progesterone levels, and the main adverse effects were reversible menstrual irregularities (73.3% at 6 months). In male (15 cases), the sperm concentration and viability were markedly decreased by THH treatment, but the sex hormone levels and erectile function did not change significantly by treatment. CONCLUSIONS: THH is effective and safe for the treatment of proteinuria in renal transplant recipients. Its primary adverse effect is reversible toxicity to reproductive organs. Further controlled clinical trials are warranted to determine the true clinical benefit of THH.

Effects of ligustrazine on ureteral obstruction-induced renal tubulointerstitial fibrosis.

Ligustrazine (LIG) is a purified and chemically identified component of the Chinese herb Ligusticum wallichii Franchat. It is a potent blocker of vasoconstriction and has strong scavenger of oxygen free radicals. We investigated the effect of LIG on renal tubulointerstitial fibrosis using a rat model of unilateral ureteral obstruction. Ligustrazine treatment significantly reduced the scores of interstitial collagen deposition, amounts of hydroxyproline, the density of myofibroblasts and macrophages, and amounts of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) compared with their level in a saline-treated control group. Using quantitative polymerase chain reaction we found that LIG treatment significantly reduced the mRNA expression of TGF-ß1, CTGF, monocyte chemoattractant protein-1 and osteopontin. Moreover, the mRNA expression of hepatocyte growth factor and bone morphogenetic protein-7 were significantly increased by LIG. In vitro, LIG inhibited the TGF-ß1-induced loss of cytokeratin-18 expression and de novo increase of the expression of α-smooth muscle actin of HK-2 cells in a dose-dependent manner, which suggested that LIG could restrain the process of epithelial-myofibroblast transition of tubular epithelial cells. This study indicates that LIG can attenuate renal tubulointerstitial fibrosis. It might be useful as a potential candidate in the treatment of chronic renal diseases.

Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method.

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid-liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC-MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C(18) column with a mobile phase consisting of methanol-water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra- and inter-batch precision of the method were less than 8.8 and 9.8%, respectively. The intra- and inter-batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3-fold after a concomitant WZ tablet dose. These results indicated that the LC-MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co-administering WZ tablet in clinical use.