Protective effect of Tritone (Livosone) on oxidative DNA damage and its hepatoprotective potential against various hepatotoxic agent in wistar rats

Aim

To evaluate antioxidant activity, DNA damage inhibition and hepatoprotecitve potential of polyherbal formulation Tritone (Livosone).

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator‐related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator‐related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25–30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of ‘occult’ mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow‐up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.     

British Society for Haematology, Slide session, Annual Scientific Meeting, Bournemouth, 2007

Eight cases discussed by experts at the 2007 Annual Scientific Meeting of the British Society of Haematology are presented as at the meeting, with a discussion of the morphological features, digital information and differential diagnosis being followed by further information and a final diagnosis. Additionally, digital slides of two of the cases were available to be viewed by the internet with the opportunity for delegates to suggest diagnoses.     

Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma

Background

Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barré syndrome, myasthenia gravis–type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravis–type syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach.

Methods

We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes.

Results

Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravis–type syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated.

Conclusions

Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks.     

Influence of RNA labeling on expression profiling of microRNAs

Although a number of technical parameters are now being examined to optimize microRNA profiling experiments, it is unknown whether reagent or component changes to the labeling step affect starting RNA requirements or microarray performance. Human brain/lung samples were each labeled in duplicate, at 1.0, 0.5, 0.2, and 0.1 μg of total RNA, by means of two kits that use the same labeling procedure but differ in the reagent composition used to label microRNAs. Statistical measures of reliability and validity were used to evaluate microarray data. Cross-platform confirmation was accomplished using TaqMan microRNA assays. Synthetic microRNA spike-in experiments were also performed to establish the microarray signal dynamic range using the ligation-modified kit. Technical replicate correlations of signal intensity values were high using both kits, but improved with the ligation-modified assay. The drop in detection call sensitivity and miRNA gene list correlations, when using reduced amounts of standard-labeled RNA, was considerably improved with the ligation-modified kit. Microarray signal dynamic range was found to be linear across three orders of magnitude from 4.88 to 5000 attomoles. Thus, optimization of the microRNA labeling reagent can result in at least a 10-fold decrease in microarray total RNA requirements with little compromise to data quality. Clinical investigations bottlenecked by the amount of starting material may use a ligation mix modification strategy to reduce total RNA requirements.     

Perspectives about complementary and alternative medicine in rheumatology

Complementary and alternative medical (CAM) treatments are considered nonmainstream therapies. The popularity and widespread usage of CAM reflects the inadequacies of the current understanding and management of rheumatic and musculoskeletal (and other) diseases despite significant progress. Better science in the future will relegate certain CAM therapies to the margins of medicine or to history and perhaps see the adoption of others into mainstream medicine. Despite the recent increased interest in CAM, particularly for rheumatic diseases, few clinically important contributions have emerged thus far.     

Guideline for investigation and management of adults and children presenting with a thrombocytosis

Acute lymphoblastic leukaemia (ALL) remains the most frequent cause of cancer‐related mortality in paediatrics and outcome is poor for patients who have high‐risk ALL or relapse. HA22 (CAT‐8015) is an immunotoxin composed of an anti‐CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A. Using a bone marrow mesenchymal cell culture assay to support ALL cell viability, we investigated the in vitro cytotoxicity of HA22 against ALL blasts from newly diagnosed (n = 13) and relapsed patients (n = 22). There was interpatient variability in sensitivity to HA22. Twenty‐four of 35 patient samples tested were sensitive (median 50% lethal concentration 3 ng/ml, range 1–80 ng/ml). Blasts from the other 11 patients were not killed by 500 ng/ml HA22. The median 50% lethal concentration was 20 ng/ml for all patients. There was no significant difference in HA22 sensitivity between diagnosis and relapse samples but peripheral blood ALL blasts were more sensitive to HA22 than those from bone marrow (P = 0·008). Thus, HA22, at concentrations achievable in patients, is highly cytotoxic to B‐lineage ALL cells. These results provide a strong rationale for clinical testing of this agent in children with drug‐resistant ALL and offers the potential to reduce morbidities of treatment while improving outcome.