Azadirachta indica as a public health tool for the control of malaria & other vector-borne diseases.

Neem-based products from Azadirachta indica have been successfully used for biological control of pest insects, mites, fungi and soil-borne nematodic root parasites. A large amount of scientific evidence is available on the potential of A. indica as a source for the development of human and animal health products. The authors champion the potential of neem-based products for the control of malaria in endemic countries, where these products are traditionally used. Neem-based larvicides and/or insecticides could complement other malaria control interventions in an integrated approach

A discrete-time Markov modulated queuing system with batched arrivals

This paper examines a discrete-time queuing system with applications to telecommunications traffic. The arrival process is a particular Markov modulated process which belongs to the class of discrete batched Markovian arrival processes. The server process is a single server deterministic queue. A closed form exact solution is given for the expected queue length and delay. A simple system of equations is given for the probability of the queue exceeding a given length.Comment: to appear Performance Evaluatio

Pregnancy in HIV-Positive Patients: Effects on Vaginal Flora

A high proportion of HIV-infected pregnant women present pathogenic organisms in their lower genital tract. This has been associated with the development of postpartum morbility, HIV transmission to the partner and offspring, and other gynaecological conditions, such as cervical dysplasia or cancer. Vaginal flora alterations can range from 47% in Western countries to 89% in Africa in pregnant HIV-positive patients, much higher than about 20% of the general population. Pathogen organism retrieval is high. As peripartum complications due to vaginal infections seem higher in HIV-positive patients, accurate investigation and treatment of such infections are strongly mandatory

Biochemical effects of urapidil on red cell membrane ion transport systems in a population of elderly essential hypertensives.

The aim of our work was to verify the effect of urapidil on membrane ion transport systems. This was a randomized, double-blind, cross-over study which evaluated the clinical and biochemical effects of urapidil (30 mg twice daily in comparison with placebo) in a group of 10 elderly hypertensive patients (3 male, 7 female ranging from 68 to 90 years, mean age 79.2 +/- 7.6 years). For the evaluation in fresh erythrocytes of principal ion transport systems (cotransport Na+/K+, countertransport Na+/Li+, Na+/K+ ATPase pump. intracellular Na+ and K+) we used the nystatin technique. We found that urapidil activated the red cell membrane ions cotransport system (basal values: 83.7 +/- 50.3 mumol Na+ RBC 1-1.h-1, after 1 month of urapidil therapy: 181.5 +/- 89.3 mumol Na+ RBC 1-1.h-1) (P less than 0.01), without significant changes in the other biochemical parameters evaluated. Our data suggest that one of the mechanisms of the urapidil antihypertensive effect could involve an increase in the membrane sodium cotransport system

SC83288 is a clinical development candidate for the treatment of severe malaria

Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca(2+) transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria

Metabolic Targeting of Breast Cancer Cells With the 2-Deoxy-D-Glucose and the Mitochondrial Bioenergetics Inhibitor MDIVI-1

Breast cancer cells have different requirements on metabolic pathways in order to sustain their growth. Triple negative breast cancer (TNBC), an aggressive breast cancer subtype relies mainly on glycolysis, while estrogen receptor positive (ER+) breast cancer cells possess higher mitochondrial oxidative phosphorylation (OXPHOS) levels. However, breast cancer cells generally employ both pathways to sustain their metabolic needs and to compete with the surrounding environment. In this study, we demonstrate that the mitochondrial fission inhibitor MDIVI-1 alters mitochondrial bioenergetics, at concentrations that do not affect mitochondrial morphology. We show that this effect is accompanied by an increase in glycolysis consumption. Dual targeting of glycolysis with 2-deoxy-D-glucose (2DG) and mitochondrial bioenergetics with MDIVI-1 reduced cellular bioenergetics, increased cell death and decreased clonogenic activity of MCF7 and HDQ-P1 breast cancer cells. In conclusion, we have explored a novel and effective combinatorial regimen for the treatment of breast cancer

Active Ageing: The Need to Address Sub-National Diversity. An Evidence-Based Approach for Italy

Artículo 13319[Abstract] While active ageing has emerged as a main strategy to address the challenges of population ageing in Europe, recent research has stressed the need to increase knowledge on within-country differences to promote active ageing through appropriate policy responses. This article draws on the Active Ageing Index (AAI) to capture recent trends in active ageing in Italy with a focus on sub-national diversity. To this end, we compute AAI breakdowns by region separately for men and women for four different years: 2007, 2009, 2012 and 2018. Then, we use linear regression to describe the geographical and sex-specific patterns of change in the AAI over the considered period. The results demonstrate the diversity of regional outcomes and trends in the active ageing of Italian men and women, indicating that the widening geographic gap deserves further consideration by national and regional authorities in designing and implementing active ageing policies. By showing the persistence of disparities in the value of the indicator to the disadvantage of women, results also suggest the need to further integrate both the gender dimension and the life-cycle perspective into active ageing strategies. This article provides an example of how the AAI can be used as a practical tool by policy makers to monitor active ageing trends and outcomes at the sub-national level, and to identify target areas that require further action

Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica.

J Nat Prod. 2010 Aug 27;73(8):1448-52. Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica. Chianese G, Yerbanga SR, Lucantoni L, Habluetzel A, Basilico N, Taramelli D, Fattorusso E, Taglialatela-Scafati O. Abstract Eight known and two new triterpenoid derivatives, neemfruitins A (9) and B (10), have been isolated from the fruits of neem, Azadirachta indica, a traditional antimalarial plant used by Asian and African populations. In vitro antiplasmodial tests evidenced a significant activity of the known gedunin and azadirone and the new neemfruitin A and provided useful information about the structure-antimalarial activity relationships in the limonoid class

Impact of repeated NeemAzal®-treated blood meals on the fitness of Anopheles stephensi mosquitoes

Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal® on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. Methods: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal® at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. Results: A dose and frequency dependent impact of NeemAzal® treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 – 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group respectively. Conclusions: The findings of this study, taken together with the accumulated knowledge on neem open the challenging prospects of designing neem-based formulations as multi-target phytomedicines exhibiting preventive, parasite transmission-blocking as well as anti-vectorial properties. Keywords: Malaria, Vectors, Neem, Azadirachtin, Transmission-blocking, Anti-vectoria