Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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A Comparison of the Effects of Oral Glutamine Dipeptide,Glutamine, and Alanine on Blood Amino Acid Availability in Rats Submitted to Insulin-Induced Hypoglycemia

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.     

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.     

Optimization of production of chlamydospores of the nematode-trapping fungus Duddingtonia flagrans in solid culture media

The large-scale production of nematophagous fungi as agents of biological control is one of the main challenges to be commercially used. In order to improve growth of microorganism in a culture medium, the addition of growth inducer is common. At the moment, the action of their addition in the mycelia growth and sporulation rate of nematophagous fungi is not known. The purpose of this trial was to evaluate the sporulation rate of Duddingtonia flagrans by adding two growth inducers, meso-inositol and Tween 80, both at 0.5 % in a traditional culture medium Sabouraud glucose agar (SGA) and also in a traditional culture medium enriched with wheat flour and milk powder. From a traditional sterile culture of D. flagrans, four groups were made: SGA; Sabouraud glucose agar–meso-inositol 0.5 %; Sabouraud glucose agar–Tween 80 0.5 %; and Sabouraud glucose agar-enriched (SGA-E). These media were placed at a constant temperature of 27 °C for 4 weeks. Following this, chlamydospores were gently rinsed off with sterile water and counted using a Neubauer haematocytometer to estimate the number of chlamydospores per millilitre of water. The addition of meso-inositol 0.5 % to SGA promoted a significant increase (p?<?0.05) in chlamydospore production obtaining an average of 51,715,000 chlamydospores per Petri dish. The highest chlamydospore concentration was observed in the SGA-E in comparison with SGA (p?<?0.01) obtaining an average of 208,760,000 chlamydospores. The aim of this study was to obtain basic knowledge regarding the effect of enriched culture medium and growth-inducing meso-inositol and Tween 80 on mycelial growth and production of chlamydospores.     

Standard immunosuppressive therapy of immune-mediated glomerular diseases

Glomerulonephritis (GN) accounts for 10%–20% of the total incident cases of end stage renal disease (ESRD), and is the third most common cause of ESRD after diabetes and hypertension in western countries. The pathogenesis of glomerulonephritis is prevalently immune mediated: humoral and cell-mediated immunity are involved, although the rationale for an etiological treatment is still lacking. In the last forty years, empirical treatment based upon the use of corticosteroids and/or immunosuppressive drugs have obtained excellent results in improving survival of both the patient and the kidney. Almost 95% of children affected by minimal change disease (MCD) achieve remission of proteinuria within 4 to 8 weeks of prednisone administration. In adults with focal segmental glomerulosclerosis (FSGS), prednisone induces complete or partial remission in the majority of patients, but a longer period of steroid treatment or the combination of calcineurin inhibitors or cytotoxic drugs can be needed. A percentage of 65%–70% of patients with idiopathic membranous nephropathy (MN) reach complete or partial remission with a 6-month course of therapy alternating glucocorticoids with alkylating agents. Glucocorticoids plus cyclophosphamide, and, on occasion, plasmapheresis are effective in 70%–90% of patients with ANCA-associated vasculitis (AAV). Fifty percent of responders relapse within the 3–5 years and currently, the mortality of AAV at 1 year exceeds 15%.This article is aimed to analyze the risk-to-benefit balance of steroids and conventional immunosuppressive regimens, focusing, for a sake of brevity, on idiopathic nephrotic syndrome (INS) and ANCA associated vasculitis.