Addition of rice bran arabinoxylan to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies (monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or stage 0/1 chronic lymphocytic leukemia): a preliminary clinical study

Hypothesis. Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design. Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods. Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results. Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion. Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies

Vitamin D in Australia : issues and recommendations

BACKGROUND A significant number of Australians and people from specific groups within the community are suffering from vitamin D deficiency. It is no longer acceptable to assume that all people in Australia receive adequate vitamin D from casual exposure to sunlight.OBJECTIVE This article provides information on causes, consequences, treatment and prevention of vitamin D deficiency in Australia. DISCUSSION People at high risk of vitamin D deficiency include the elderly, those with skin conditions where avoidance of sunlight is required, dark skinned people (particularly women during pregnancy or if veiled) and patients with malabsorption, eg. coeliac disease. For most people, deficiency can be prevented by 5&ndash;15 minutes exposure of face and upper limbs to sunlight 4&ndash;6 times per week. If this is not possible then a vitamin D supplement of at least 400 IU* per day is recommended. In cases of established vitamin D deficiency, supplementation with 3000-5000 IU per day for at least 1 month is required to replete body stores. Increased availability of larger dose preparations of cholecalciferol would be a useful therapy in the case of severe deficiencies. * 40 IU (international units) = 1 &micro;g<br /

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Method: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. Results: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. Discussion: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis

Developmental and Molecular Characterization of Emerging β- and γδ-Selected Pre-T Cells in the Adult Mouse Thymus

The first checkpoint in T cell development, β selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating β selection, concomitant with intracellular TCR-β expression. Clonal analysis determined that CD27^(high) DN3 cells generate CD4^+CD8^+ progeny with more than 90% efficiency, faster and more efficiently than the CD27^(low) majority. CD27 upregulation also occurs in γδ-selected DN3 thymocytes in TCR-β−/− mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-γδ cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with β selection, and with γδ selection. γδ selection induces higher CD5, Egr, and Runx3 expression as compared to β selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing αβ and γδ T-lineage cells

CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue

Rapid increases in obesity in Jamaica, compared to Nigeria and the United States

<p>Abstract</p> <p>Background</p> <p>Weight gain in adulthood is now common in many populations, ranging from modest gains in developing countries to a substantial percentage of body weight in some Western societies. To examine the rate of change across the spectrum of low to high-income countries we compared rates of weight change in samples drawn from three countries, Nigeria, Jamaica and the United States.</p> <p>Methods</p> <p>Population samples from Nigeria (n = 1,242), Jamaica (n = 1,409), and the US (n = 809) were selected during the period 1995–1999 in adults over the age of 19; participation rates in the original survey were 96%, 60%, and 60%, respectively. Weight in (kg) was measured on 3 different occasions, ending in 2005. Multi-level regression models were used to estimate weight change over time and pattern-mixture models were applied to assess the potential effect of missing data on estimates of the model parameters.</p> <p>Results</p> <p>The unadjusted weight gain rate (standard error) was 0.34(0.06), 1.26(0.12), 0.34(0.19) kg/year among men and 0.43(0.06), 1.28(0.10), 0.40(0.15) kg/year among women in Nigeria, Jamaica, US, respectively. Regression-adjusted weight change rates were significantly different across country, sex, and baseline BMI. Adjusted weight gain in Nigeria, Jamaica and US was 0.31(0.05), 1.37(.04), and 0.52(0.05) kg/year respectively. Women in Nigeria and the US had higher weight gains than men, with the converse observed among Jamaicans. The obese experienced weight loss across all three samples, whereas the normal weight (BMI < 25) had significant weight gains. Missing data patterns had an effect on the rates of weight change.</p> <p>Conclusion</p> <p>Weight change in sample cohorts from a middle-income country was greater than in cohorts from either of the low- or high-income countries. The steep trajectory of weight gain in Jamaica, relative to Nigeria and the US, is most likely attributable to the accelerating effects of the cultural and behavioral shifts which have come to bear on transitional societies.</p

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

The effect of curcumin (as Meriva) on absolute lymphocyte count (ALC), NK cells and T cell populations in patients with stage 0/1 chronic lymphocytic leukemia

Purpose: To determine the effect of curcumin (as Meriva) on absolute lymphocyte count (ALC), T cell populations and NK cells in patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) over a period of six months. Experimental Design: Twenty-one patients with significant lymphocytosis (\u3e20 x 109 lymphocytes/L) and stage 0/1 CLL were recruited into the study and received oral curcumin 2 grams/day. Blood samples were collected at baseline and at 2 monthly intervals for six months for full blood count, leukocyte surface antigens, liver function, serum biochemistry, immunoglobulins, CRP and ESR. A positive biologic response was defined as a reduction in the ALC of more than 20% from pre-treatment levels. Results: Four patients (20%) demonstrated more than 20% decrease in ALC, three of whom had lower ALC at the end of the study as compared to baseline. The decrease in ALC was accompanied by an increase in CD4, CD8 and NK cells. No demonstrable response was seen in seventeen patients (80%) who exhibited stable, fluctuating or increasing ALC during the study. Conclusion: A subgroup of stage 0/1 CLL patients may be responsive to curcumin therapy. The beneficial response appears to be immunomodulated

Curcumin enhances the cytotoxic and chemosensitising effects of lenalidomide in human multiple myeloma cells

Background: Curcumin, the active component of the Curcuma longa plant, has been shown to potentiate the effect of the immunomodulatory drugs (IMiDs) thalidomide and Bortezomib against human myeloma cell lines and a nude mice model. Its effect on the other IMid, lenalidomide, has not been evaluated. This study aims to investigate the mechanism of action of curcumin and its potential ability to positively interact with lenalidomide. Method: we designed an in-vitro study to investigate the cytotoxic and chemo-sensitising effects of curcumin alone and in combination with lenalidomide on the human myeloma H929 cell line. Results: Incubation of H929 cells with curcumin (30mM) or lenalidomide (2.5 mM) for 3 days resulted in 26.35% (±1.06) and 30.81%(±2.98) apoptotic cells respectively. When 30 mM curcumin was combined with 2.5 mM lenalidomide, 50.4% (±3.37) apoptotic cells were detected by flow cytometry and the increase was significant compared to either curcumin alone or lenalidomide alone (anova p = 0.0026). Furthermore, gene analysis studies show that curcumin enhances the cytotoxic effect of lenalidomide via suppression of the cereblon and multi-drug resistant genes. Conclusion: Curcumin exerts a cytotoxic effect additive to that of lenalidomide on H929 myeloma cells, and it also enhances the chemo-sensitizing effects of this agent