Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

The medicinal benefit of salts of fumaric acid and its esters (FAE), known as fumarates (mono and dimethyl fumarate), was realized many years ago. Early on, FAE were derived from plants and mushrooms (e.g., Fumaria officinalis, Boletus fomentarius var. pseudo-igniarius). The FAE containing formulation Fumaderm® was licensed in Germany for the treatment of psoriasis in 1994. Recently, a clinical formulation of dimethyl fumarate known as BG12 (Tecfidera) was approved for use in the United States, New Zealand, Australia, European Union, Switzerland, and Canada for the treatment of multiple sclerosis. Others and we have assessed the potential benefit of FAE in a number of disease conditions that are diverse with respect to etiology but unified with regard to the involvement of inflammation and oxidative stress. Hence, a FAE-based drug with robust anti-oxidative and anti-inflammatory effects that is already US-FDA approved is a perfect contender for repurposing and rapid clinical implementation for their management. There is a burgeoning literature on the use of FAE in the prevention and treatment of diseases, other than psoriasis and MS, in which oxidative stress and/or inflammation are prominent. This chapter highlights critical information gleaned from these studies, exposes lacunae of potential importance, and provides related perspectives

Growth and yield of Vigna radiata L.) under Terminalia arjuna and Mitragyna parvifolia based agrisilvicultural system

The present investigation was carried out in an agrisilvicultural system with treatments involving silvicultural component of 20 years old Terminalia arjuna Bedd. (Arjun) and Mitragyna parvifolia Korth (Kalam) intercropped with agricultural component of four varieties of green gram (Vigna radiata L.) viz. Pusa Vishal, GM-3, GM-4 and K-851. All the varieties of green gram were compared for growth and yield parameters like plant height (cm), number of leaves, number of branches per plant, total grain yield per plant as well as per plot at harvestablestage under Arjuna and Kalam trees. All the varieties of green gram performed superior in terms of number of leaves, numbers of branches, grain yield (per plant and per plot basis) under open condition as compared to crops under Arjuna and Kalam. However, only the plant height was found to be highest under Arjun, followed by Kalam trees. Among all the varieties tested, K-851 variety showed superiority for number of leaves (12.31) and number of branches per plant (3.96) and grain yield (2.66 gm per plant and 0.80 kg per plot) as compared to other varieties (at P=0.05). Therefore, this variety is suggested to grow in south Gujarat condition. Further, comparatively lower yield of crop under tree cover could be due to shade effect, which can be managed by regular pruning of tree branches

Effects of gamma rays on germination and growth in Jatropha curcas L.

The present investigation was carried out at the Forestry Research Farm, Navsari Agricultural University; Navsari to evaluate the gamma rays at 10 kR, 20 kR and 30 kR induced variability in Jatropha curcas L. on germination, growth and yield for seven Jatropha genotypes (Phule J-1, Urlikanchan, Hansraj, SKN Big, Chhatrapati, Hansot and MPJ-55). The significantly maximum germination percentage (66.96%), seedling survival (74.18%), seedling collar diameter (0.958cm), shoot length (49.442cm), number of leaves per seedling (7.757) and leaf area (37. 58)was observed in Chhatrapati genotype during nursery stage. While low rate of gamma rays treatment (10 kR) had stimulatory effect for germination percentage, seedling survival, seedling collar diameter, shoot length, number of leaves per seedling and leaf area. However, higher gamma rays doses (30 kR) drastically reduced all studied characters. The interaction effect of genotype and gamma rays were significant for number of leaves per seedling. Further, it was not significant in other traits like germination percentage, seedling survival, seedling collar diameter, shoot length and leaf area

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy

Efficacy of different oils used for the extraction of annatto colour from the seeds of Bixa orellana L.

Annatto, a naturally obtained colour is a potential and valuable Non Wood Forest Product (NWFP). It is obtained from the seeds of plant species Bixa orellana L. The present experiment was carried out to find the efficacy of different oils used for annatto colour extraction. Experiment was started with the pretreatment of seeds of B. orellana with soaking in water at 0%, 50%, 100% and 150% (v/w) for 24 hrs at room temperature and colour extraction with castor oil at 100°C showed that maximum bixin (%) was found from the pretreated seeds with 50% (v/w) water soaking i.e., 0.46% bixin. Similarly for oil soluble annatto extraction method, the maximum extraction of bixin (0.99 %) was found with castor oil at 120°C for 1 hr and least bixin (0.03 %) was recorded with mustard oil at 60oC temperature for 1 hr. Sesame oil and ground nut oil were also showed better extractability. Out of different treatments, castor oil at 120°C for 1 hr gave better result with respect to bixin extraction as compared to others

Clonal evaluation for early growth performance of Eucalyptus in South Gujarat, India

This study was carried out in College of Forestry, Navsari Agricultural University, Navsari, Gujarat. Total 20 clones having age of 5 ½ years were selected for early growth evaluation at field condition. There was a significant variation (P < 0.05) among 20 clones of Eucalyptus for growth parameters viz., tree height, DBH, mid-diameter, form quotient and volume of standing tree. Tree height varied from 18.5 to 23.6 m with DBH range of 11.47 to 16.07 cm. Mid-diameter indirectly helps to assess the tapering of tree and it ranged from 6.99 to 10.57 cm among 20 clones. The form quotient was used while calculation of volume of Eucalyptus clones. The form quotient varied between 0.58 and 0.71 with overall mean of 0.63 at studied site. Volume of standing tree ranged from 0.12 to 0.28 m3. The overall results showed that clones such as C12 (P2045), C17 (B2253), C4 (P413), C8 (P526), C7 (P498), C16 (SRO16) and C11 (P3020) performed superior for early growth attribute and stem form and these clones suggested for large scale plantation in South Gujarat region

A Cold Atom Radio-Frequency Magnetometer

We propose and demonstrate a radio-frequency atomic magnetometer with sub-Doppler laser cooled rubidium-87. With a simple and compact design, our system demonstrates a sensitivity of 330 pT/ √ Hz in an unshielded environment, thus matching or surpassing previously reported cold atoms designs. By merging the multiple uses and robustness of radio-frequency atomic magnetometers with the detailed control of laser cooling, our cold atom radio-frequency magnetometer has the potential to move applications of atomic magnetometry to high spatial resolution. Direct impact in metrology for applied sciences, materials characterization, and nanotechnology can be anticipated

Pharmacists in Pharmacovigilance: Can Increased Diagnostic Opportunity in Community Settings Translate to Better Vigilance?

The pharmacy profession has undergone substantial change over the last two to three decades. Whilst medicine supply still remains a central function, pharmacist’s roles and responsibilities have become more clinic and patient focused. In the community (primary care), pharmacists have become important providers of healthcare as Western healthcare policy advocates patient self-care. This has resulted in pharmacists taking on greater responsibility in managing minor illness and the delivery of public health interventions. These roles require pharmacists to more fully use their clinical skills, and often involve diagnosis and therapeutic management. Community pharmacists are now, more than ever before, in a position to identify, record and report medication safety incidents. However, current research suggests that diagnostic ability of community pharmacists is questionable and they infrequently report to local or national schemes. The aim of this paper is to highlight current practice and suggest ways in which community pharmacy can more fully contribute to patient safety

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg−1wk−1) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose–response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg−1wk−1cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl−1respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing. © 2001 Cance Cancer Research Campaig

Establishing a clinical phenotype for cachexia in end stage kidney disease - study protocol.

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education