When are apparently non-clonal abnormalities in bone marrow chromosome studies actually clonal?

The observation of an apparently non-clonal abnormal cell in a cytogenetic study for a hematologic neoplasm opens the possibility of a small, or slowly proliferating, abnormal clone. Many laboratories analyze additional cells or reflex to fluorescence in situ hybridization (FISH) to evaluate this possibility further. In a retrospective study of 500 cases with a non-clonal abnormal cell identified in a 20-cell analysis, we found that the benefit of additional metaphase analysis was limited to specific categories of abnormal karyotypes, including those with a complex karyotype or a classic abnormality known to be a recurring finding in hematologic neoplasms, and excluding all other categories.     

Influence of probe pressure on the diffuse correlation spectroscopy blood flow signal: extra-cerebral contributions

A pilot study explores relative contributions of extra-cerebral (scalp/skull) versus brain (cerebral) tissues to the blood flow index determined by diffuse correlation spectroscopy (DCS). Microvascular DCS flow measurements were made on the head during baseline and breath-holding/hyperventilation tasks, both with and without pressure. Baseline (resting) data enabled estimation of extra-cerebral flow signals and their pressure dependencies. A simple two-component model was used to derive baseline and activated cerebral blood flow (CBF) signals, and the DCS flow indices were also cross-correlated with concurrent Transcranial Doppler Ultrasound (TCD) blood velocity measurements. The study suggests new pressure-dependent experimental paradigms for elucidation of blood flow contributions from extra-cerebral and cerebral tissues.OCIS codes: (170.3880) Medical and biological imaging, (170.2655) Functional monitoring and imaging, (170.3660) Light propagation in tissues, (170.6480) Spectroscopy, speckle     

Elbow nerves: normal sonographic anatomy and identification of the structures potentially associated with nerve compression. A short pictorial-video article

Purpose

To demonstrate usefulness of ultrasonography evaluation of the nerves of the elbow and of the structures that more frequently might cause its compression.

Materials and methods

Anatomic course of nerves, muscles, tendons, fibrous structures and bursae potentially associated with nerve compression syndromes were evaluated. Informed consent was obtained from each volunteer.

Results

Ulnar, median and radial nerves are always evaluable with ultrasonography as well as muscles and tendons potentially associated with nerve compression. The bursae cannot be sonographically explored unless distended by fluid.

Conclusion

Ultrasonography is a reliable method for the evaluation of the nerves of the elbow and of the structures that might cause its compression.

Electronic supplementary material

The online version of this article (doi:10.1007/s40477-013-0029-6) contains supplementary material, which is available to authorized users.     

The ARMS-D out performs the SDSCA,but both are reliable,valid, and predict glycemic control

Aims

The Adherence to Refills and Medications Scale (ARMS) has been associated with objective measures of adherence and may address limitations of existing self-report measures of diabetes medication adherence. We modified the ARMS to specify adherence to diabetes medicines (ARMS-D), examined its psychometric properties, and compared its predictive validity with HbA_1C against the most widely used self-report measure of diabetes medication adherence, the Summary of Diabetes Self-Care Activities medications subscale (SDSCA-MS). We also examined measurement differences by age (<65 vs. ≥65 years) and insulin status.

Methods

We administered self-report measures to 314 adult outpatients prescribed medications for type 2 diabetes and collected point-of-care HbA_1C.

Results

One of the 12-item ARMS-D items was identified as less relevant to adherence to diabetes medications and removed. The 11-item ARMS-D had good internal consistency reliability (α = 0.86), maintained its factor structure, and had convergent validity with the SDSCA-MS (rho = −0.52, p < 0.001). Both the ARMS-D (β = 0.16, p < 0.01) and the SDSCA-MS (β = −0.12, p < 0.05) independently predicted HbA_1C after adjusting for covariates, but this association did not hold among participants ≥65 years in subgroup analyses. There were no differences in ARMS-D or SDSCA-MS scores by insulin status, but participants on insulin reported more problems with adherence on two ARMS-D items (i.e., feeling sick and medicine costs).

Conclusions

The ARMS-D is a reliable and valid measure of diabetes medication adherence, and is more predictive of HbA_1C than the SDSCA-MS, but takes more time to administer. The ARMS-D also identifies barriers to adherence, which may be useful in research and clinical practice.     

Reliability and validity of the Chinese version of the Scale for Assessment and Rating of Ataxia

Background The Scale for the Assessment and Rating of Ataxia (SARA) was shown to be a reliable and valid measurement for patients with spinocerebellar ataxia (SCA).The Brazilian version and the Japanese version of SARAwere favorable for good reliability and validity.This study aimed to translate SARA into Chinese and test its reliability and validity in measurement of cerebellar ataxia.Methods SARA was translated into Chinese.A total 39 patients with degeneration cerebellar ataxia were evaluated independently by two neurologists with the Chinese version of SARA.Then the patients were evaluated by one of above neurologists with International Cooperative Ataxia Rating Scale (ICARS).The statistical analyses were performed using SPSS 17.0 for Windows.Results The Cronbach's alpha coefficient of the Chinese version of SARA was 0.78,which represents a good internal consistence.The correlation coefficient of the Chinese version of SARA scores between the two evaluators was 0.86,illustrating that the inter-rater reliability of Chinese version of SARA was good.The correlation coefficient between the Chinese version of SARA and ICARS was 0.91,illustrating that the criterion validity of Chinese version of SARA was not bad.Conclusions The Chinese version of SARA is reliable and effective for the assessment of degeneration cerebellar ataxia.Compared with ICARS,the evaluation of Chinese version of SARA is more objective,the assessment time is shortened,and the maneuverability is better.     

Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life,brain delivery and efficacy in glioblastoma cells

Noscapine crosses blood–brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 ± 9.3-nm and 80.5 ± 8.9-nm containing 80.4 ± 3.2% and 83.6 ± 1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH ~ 4.5. Further, a decrease in IC₅₀ (Nos; 40.5 μM > Nos-SLN; 27.2 μM > 20.8 μM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~ 11-fold and ~ 5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P < 0.05) deposits 400.7 μg/g and 313.1 μg/g of Nos in comparison to 233.2 μg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer.From the Clinical EditorThis report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer.     

An update on PTEN modulators – a patent review

ABSTRACT

Introduction: A multitude of cellular and physiological functions have been attributed to the biological activity of PTEN (Phosphatase and tensin homolog) such as inhibiting angiogenesis, promoting apoptosis, preventing cell proliferation, and maintaining cellular homeostasis. Based on whether cell growth is needed to be initiated or to be inhibited, enhancing PTEN expression or seeking to inhibit it was pursued.

Areas covered: Here the authors provide recent updates to their previous publication on ‘PTEN modulators: A patent review’, and discuss on new specificities that affirm the therapeutic potential of PTEN in promoting neuro-regeneration, stem cell regeneration, autophagy, bone and cartilage regeneration. Also, targeting PTEN appears to be effective in developing new treatment strategies for Parkinson’s disease, Alzheimer’s disease, macular degeneration, immune disorders, asthma, arthritis, lupus, Crohn’s disease, and several cancer types.

Expert opinion: PTEN mainly inhibits the PI3k/Akt pathway. However, the PI3k/Akt pathway can be activated by other signaling proteins. Thus, novel treatment strategies that can regulate PTEN alone, or combinational treatment approaches that can induce PTEN and simultaneously affect downstream mediators in the PI3K/Akt pathway, are needed, which were not investigated in detail. Commercial interests associated with molecules that regulate PTEN are discussed here, along with limitations and new possibilities to improve them.     

Effect of exposure to fentanyl aerosol in mice on breathing pattern and respiratory variables

The breathing pattern of mice that were exposed to fentanyl aerosol was studied (2.7, 5.7, 6.0, 10.0, and 23.6 μg/m³; for 1 hour), using dimethyl sulfoxide as a vehicle. This study was conducted in a head-only exposure assembly. Body plethysmographs connected to a volumetric pressure transducer were used to capture the respiratory signals, and an on-line computer program capable of recognizing the changes in the breathing pattern was used for monitoring the respiratory pattern. The response of mice to fentanyl exposure was found to be concentration dependent. A lower concentration (2.7 μg/m³) showed fast recovery and no mortality, while 100% mortality was observed at a higher concentration (23.6 μg/m³). No sensory, pulmonary irritation, and airway limitation in mice was observed, and death occurred probably due to respiratory depression. The concentration that decreased 50% of the respiratory frequency (RD₅₀) was estimated to be 6.4 μg/m³. The extrapolated human threshold limit value, calculated from the RD₅₀ value, was found to be 0.192 μg/m³. The concentration that caused 50% mortality in exposed mice (LC₅₀) was estimated to be 8.8 μg/m³. This study shows that aerosolized fentanyl does not cause sensory and pulmonary irritation, and since the RD₅₀ and LC₅₀ are very close with a low safety margin, this type of sedative should not be used as an incapacitating agent.     

Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A

Objectives:

The present study was undertaken to evaluate the radioprotective and cytoprotective potential of cordifolioside-A, a primary active constituent of n-butanol fraction of Tinospora Cordifolia (NBTC) against 4 Gy-γ radiation in mice and cyclophosphamide induced genotoxicity.

Materials and Methods:

Presence of cordifolioside-A in NBTC stem ethanolic extract was confirmed by high performance thin layer chromatography (HPTLC) analysis. Radioprotective activity was evaluated at 80 and 120 mg/kg, intraperitoneal (i.p.) dose of NBTC administered 15 days prior to whole body radiation exposure by observing survival rate, change in body weight, hematology, spleen colony forming unit (CFU), and micronucleus (MN) expression. Cytoprotective activity of NBTC was evaluated at 5, 10, and 15 mg/ml concentrations on Allium cepa root meristem growth against cyclophosphamide.

Results:

HPTLC analysis of standard cordifolioside A, and NBTC confirmed the presence of cordifolioside-A in NBTC with the retention factor value of 0.86. Administration of NBTC (120 mg/kg, i.p.) produced significant protection against radiation in terms of increased survival rate, body weight retention, hematological parameters, spleen CFU assay (P < 0.01), and decreased MN expression (P < 0.01). Cytoprotectivity was observed maximally at 10 mg/ml NBTC concentration with significant increase in root growth (P < 0.01), non-toxic mitotic index (MI) (65.9%) and lesser chromosomal aberrations (15.4%). NBTC at 10 mg/ml concentration showed very few C-anaphase compared to aberrations like fragmentation, C-anaphase, multipolarity and sticky chromosome in cyclophosphamide alone.

Conclusion:

The results suggest that enriched NBTC containing cordifolioside-A has a potential in vivo radioprotective effect as well as in vitro cytoprotective activity.KEY WORDS: Cordifolioside-A, cytoprotective activity, radioprotective activity, Tinospora cordifolia