Sarcoid-Like Reaction in the Kidney Following Rituximab for Mantle Lymphoma in a 60-Year-Old Man.

The sarcoid-like reaction is a rare autoinflammatory disease that can affect lymph nodes or organs but does not meet the diagnostic criteria for systemic sarcoidosis. Several drug classes have been associated with the development of a systemic sarcoid-like reaction, which defines drug-induced sarcoidosis-like reactions and can affect a single organ. Anti-CD20 antibodies (rituximab) have rarely been reported as responsible for this reaction and this adverse effect has mainly been described during the treatment of Hodgkin's lymphoma. We report a unique case of a sarcoid-like reaction complicating rituximab following the treatment of a mantle cell lymphoma and interesting only the kidney. The 60-year-old patient presented with severe acute renal failure 6 months after the end of his r-CHOP protocol and the urgent renal biopsy revealed acute interstitial nephritis rich in granulomas without caseous necrosis. After ruling out other causes of granulomatous nephritis, a sarcoid-like reaction was retained since infiltration was limited to the kidney. The temporal relationship between rituximab administration and the sarcoid-like reaction onset in our patient supported the diagnosis of a rituximab-induced sarcoidosis-like reaction. Oral corticosteroid treatment led to rapid and lasting improvement in renal function. Clinicians should be warned of this adverse effect and regular and prolonged monitoring of renal function should be recommended during the follow-up of patients after the end of treatment with rituximab.

Bromuconazole fungicide induces cell cycle arrest and apoptotic cell death in cultured human colon carcinoma cells (HCT116) via oxidative stress process.

BACKGROUND: Bromuconazole, a fungicide belonging to the triazole family, is a plant protection product used to control, repel or destroy fungi that may develop on crops. We investigated the pro-apoptotic effect of bromuconazole and the role of oxidative stress in the death mechanism induced by this fungicide in this study. METHODS: The human colon HCT116 cell line was treated with Bromuconazole (IC50/4, IC50/2, and IC50) for 24 h. Cells were collected and analysed for biomarkers of apoptotic cell death and oxidative stress as well as for the assessment of genotoxic damage. RESULTS: Our study showed that bromuconazole caused a concentration-dependent increase in cell mortality with an IC50 of 180 µM. Bromuconazole induced cell cycle arrest in the G0/G1 phase and DNA synthesis inhibition. The Comet assay showed that bromuconazole caused DNA damage in a concentration-dependent manner. Bromuconazole-induced apoptosis was observed by, Annexin-V/FITC-PI and BET/AO staining, by mitochondrial membrane depolarisation, and by increased caspase-3 activity. In addition, bromuconazole induced a significant increase in ROS and lipid peroxidation levels and a disruption in SOD and CAT activities. N-acetylcysteine (NAC) strongly prevents cytotoxic and genotoxic damage caused by bromuconazole. CONCLUSION: Bromuconazole toxicity was through the oxidative stress process, which causes DNA damage and mitochondrial dysfunction, leading to cell cycle arrest and apoptotic death of HCT116 cells.

Bromuconazole exposure induced cell cycle arrest in the G0/G1 in HCT116 cells.Bromuconazole caused DNA synthesis inhibition and degradation.Bromuconazole-induced Annexin-V/FITC-PI and BET/AO positive staining, increased caspase-3 activity and MMP.Bromuconazole enhances ROS, MDA levels and disruption of CAT and SOD activities.

Evaluation of hepatotoxicity and nephrotoxicity induced by fenpyroximate in subchronic-orally exposed Wistar rats.

BACKGROUNDS: Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain. The aim of this work was to explore the hepatotoxic and nephrotoxic effects of FEN on Wistar rats. METHODS: The study involved five groups: a control group and four groups treated with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 consecutive days. Histological examination and biochemical analysis of hepatic and renal biomarkers were performed. The malondialdehyde (MDA), protein carbonyl levels, and antioxidant enzymes activities were measured. Comet assay was conducted to explore FEN genotoxicity. RESULTS: FEN induced a disturbance of the hepatic and renal functions as evidenced by an increase in AST, ALT, ALP, creatinine, and uric acid levels and histopathological modifications in the two examined tissues. FEN increased hepatic and renal lipid peroxidation and protein oxidation. The activities of liver and kidney SOD, CAT, GPX, and GST are increased significantly in FEN-treated rats at doses of 2 and 4 mg/kg bw. However, with the dose of 8 mg/kg bw of FEN, these activities are decreased. Moreover, FEN increased DNA damage in a dose-dependent manner. CONCLUSION: FEN was hepatotoxic and nephrotoxic very likely through induction of oxidative stress.

Long-term clinical outcomes of peritoneal dialysis patients: 10-year experience of a single unit from Tunisia.

Published data on the outcome of maintenance peritoneal dialysis (PD) since the initiation of PD in Tunisia is poor. The purpose of this study is to report long-term clinical outcomes of PD patients through a 10-year experience at a single unit. This is a retrospective review of the medical records of 182 PD patients who were followed up from January 2006 to June 2016. All patients were followed till death, renal transplant, switch over to hemodialysis (HD) or the end of the study in June 2016. The mean age of the incident patients was 43.93 ± 16.95 years. Nineteen (10.4%) were aged >65 years and 59.3% were male. The average duration of follow-up was 27.75 ± 26.18 months. The mean duration of PD treatment was 27.75 ± 26.18 months. There were 186 episodes of peritonitis that occurred over the total study period (54 episodes during the 1st year). The overall incidence of peritonitis during the 10-year study period was 1 per 27.25 patient months. Mechanical complications were noted in 31.2% of cases. Thirty- two (17.6%) patients had catheter displacement. Only 26 cases of hemoperitoneum (14.3%) were recorded. Death occurred in 23.1% of cases. Twenty-two patients (27.5%) were transplanted; 56 patients (70%) were transferred to HD, one patient had renal recovery and one case had voluntarily interrupted PD. In Kaplan-Meier curves of residual renal function (RRF) loss, there was a significant difference between peritonitis group and peritonitis-free group (P = 0.01). Technique and patient survival were associated with diabetes with a significant difference. The main cause of technique failure was peritonitis (61.4%). Moreover, the main repertoried causes of death were cardiovascular and septic causes. The mortality of diabetic and elderly PD patients was higher than mortality in nondiabetic and nonelderly groups, respectively, in our study. Peritonitis was associated with loss of RRF and technique failure.

Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells.

Cisplatin is an effective agent against various solid tumors. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Therefore, strategies for minimising the toxicity of cisplatin are of a clinical interest. The aim of this study was to investigate the protective effect of recombinant human erythropoietin (rhEPO) against the cytotoxicity and apoptosis induced by cisplatin in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to cisplatin (pre-treatment), (ii) cells were treated with rhEPO and cisplatin simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to cisplatin (post-treatment). Our results showed that rhEPO reduced cisplatin-induced cell mortality. Besides, rhEPO administration prevented cisplatin-induced DNA damage. Furthermore, rhEPO decreased the caspase-3 activity and pro-apoptotic factors levels (p53 and Bax) induced by cisplatin. It increased also the expression of the anti-apoptotic factor Bcl2 in Vero cells. Altogether, our results suggest a protective action of rhEPO against cisplatin cytotoxicity and genotoxicity via an anti-apoptotic process. The most protective effect was observed with rhEPO when it was administrated 24 h before cisplatin treatment.