Margaret I Rolfe

An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects

Aim:  Renal fibrosis is central to progression of most chronic renal pathologies. Antioxidants that protect the tubular epithelium and anti‐fibrotics that induce apoptosis of pro‐fibrotic myofibroblasts without adversely affecting tubular epithelium may slow progression of renal fibrosis, while toxic substances may exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular epithelial cells (NRK52E) to determine their potential value as therapeutic agents in renal fibrosis involving oxidative stress.

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

BackgroundOxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial.MethodsThe study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function.ResultsA significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression.ConclusionThis study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).Trial RegistrationAustralian and New Zealand Clinical Trials Register: ACTRN12605000258651

Memory loss after adjuvant chemotherapy for breast cancer: a preliminary analysis of mediating variables utilizing cross-sectional correlations and multilevel longitudinal analysis

General Sessions [#11-82] S5–S23 Poster Discussion Sessions [#101-511] S24–S40 Poster Session I [#1001-1119] S41–S83 Poster Session II [#2001-2121] S84–S125 Poster Session III [#3001-3113] S126–S165 Poster Session IV [#4001-4117] S166–S206 Poster Session V [#5001-5119 (excl. 5015)] S207–S246 Poster Session VI [#6001-6119 plus 5015] S247–S287 Author index for abstracts S288–S302

An in vitro study of the effects of medicinal plant extracts on renal cells: Potential therapeutic and toxic effects of herbal extracts

Coexistence of anti-glomerular basement membrane (anti-GBM) antibody and antineutrophil cytoplasmic antibody (ANCA) with myeloperoxidase specificity (MPO-ANCA) exists in a substantial proportion of patients with rapidly progressive glomerulonephritis (RPGN). There is sparse literature on these ‘double positive’ RPGN, without consensus on the different approaches for optimal preservation of renal function and prevention of pulmonary hemorrhages. A previously healthy 71 year old female presented with persistent peripheral edema and general malaise. Serum creatinine level of 8.5 mg/dl and serum potassium level of 6.8 mEq/l prompted emergent hemodialysis. Antibody panels revealed both antiGBM antibodies (142 EU, normal range 0.0–9.0 EU) and MPO-ANCA (13.3 U/ ml, normal range 0.0–8.9 U/ml). Indirect immunofluorescent assay using patient’s sera showed perinuclear staining, confirming the P-ANCA. Renal biopsy revealed histologic features of cellular crescents and global sclerosis, but absence of immunoglobulin deposition in the glomerulus. Typical IgG linear deposition was illustrated in normal human glomeruli using patient’s sera. We started her on steroid and plasma exchange therapy based on the recent findings that ANCA is responsible for pulmonary hemorrhage. Her serum anti-GBM antibody and MPOANCA decreased to subclinical levels after one month of therapy. She was free of pulmonary complication, although persistently dialysis dependent. More work is needed to define the clinical approach for patients with simultaneous ANCA and anti-GBM.