National mass drug administration costs for lymphatic filariasis elimination

Background

Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.

Methodology/Principal Findings

To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.

Conclusions/Significance

MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.     

Efficacy of Ginkgo biloba on Vaginal Estrous and Ovarian Histological Alterations for Evaluating Anti‐Implantation and Abortifacient Potentials in Albino Female Mice

Ginkgo extract, EGb 761 is known as a vasoregulatory variable for the conventional reproduction therapy. EGb 761 was orally administered in 0 (control), 3.7, 7.4, and 14.8 mg/kg bw/day for 28 days (thereafter mated with normal fertile male), from day 1 to day 7 of pregnancy or from the 10th to 18th day of pregnancy, respectively. Vaginal smears were performed daily. On 20th day of pregnancy, the females were killed by cervical dislocation and their kidneys, liver, brain, placenta, spleen and ovaries were removed and weighed. The ovaries were prepared for histological examinations, and then ovarian follicles were counted. Maternal toxicity, estrous cycle, reproductive hormones, ovarian follicle counts, resorption index, implantation index, fetal viability and fetuses, and placenta mean weights were evaluated. There was a dose‐dependent ovarian toxic effect of EGb 761. Ovarian follicle counts, resorption index, implantation index, fetal viability were significantly reduced in 14.8 mg/kg bw/day dose. Treatment with 14.8 mg/kg bw/day EGb 761 induced disruption of estrous cycle and caused maternal toxicity, in addition to fetal toxicity. Therefore, the data obtained indicate that Ginkgo biloba extract at 14.8 mg/kg bw/day dose level exhibit toxic effect on reproductive cyclicity and could have anti‐implantation and abotifacient properties in female mice.     

Endogenous cytokinins in vernalized winter wheat grains

Summary The soybean callus assay was used to study the effect of vernalization on the endogenous cytokinin levels of the grains of winter wheat (Triticum vulgare L.), cv. Ferto and Fema. Vernalization of the grains was carried out at 3° C in the dark for 0, 9, 18, 27, 36 and 45 days. Cytokinin activities could be detected in both the aqueous and butanol extracts of vernalized grains of both cultivars. It is suggested that flowering of winter wheat may involve changes in the levels of endogenous cytokinins during vernalization.     

Protein content and amino acids composition of bee-pollens from major floral sources in Al-Ahsa,eastern Saudi Arabia

Protein content and amino acids composition of bee-pollens from major pollen floral sources in Al-Ahsa, Saudi Arabia were determined to investigate the nutritive value of pollen protein relative to requirements of honeybees and adult humans. The major pollen sources were alfalfa, date palm, rape, summer squash, and sunflower. Bee-pollens from alfalfa and date palm showed high content of crude protein and amino acid concentrations. Bee-pollen from sunflower had low content of those components. Eighteen amino acids were found in bee-pollens from the five major floral sources. The highest concentrations of individual amino acids valine, leucine, isoleucine, phenylalanine and proline were obtained from alfalfa bee-pollen; lysine, arginine, cysteine, tryptophan and tyrosine from date palm; methionine, histidine, glycine and alanine from summer squash; threonine, serine and glutamic acid from sunflower; and aspartic acid from rape bee-pollen. The amino acid composition obtained from sunflower bee-pollen showed the lowest concentrations of the essential amino acids: isoleucine, leucine, methionine, phenylalanine and valine. Apart from methionine, arginine and isoleucine, the essential amino acids of bee-pollen from alfalfa, date palm, summer squash and rape exceeded the honeybees’ requirements. Methionine was the limiting amino acid in bee-pollens from the five selected sources. Concentrations of essential amino acids in the tested bee-pollens were variable and significantly correlated to their botanical origin of pollen. Bee-pollens from alfalfa, date palm and summer squash was found to be rich source of protein and amino acids for bees and for humans.     

An improved method for micropropagation and regeneration of date palm (Phoenix dactylifera L.)

We developed a novel large-scale micropropagation pathway for date palm (Phoenix dactylifera L.) based on organogenesis. We obtained organogenic stems from shoot tip explants of the Moroccan date palm cultivar Najda, and investigated shoot proliferation from these organogenic stems in vitro on various media; Beauchesne medium (BM) and Murashige and Skoog medium (MS) at full-strength, half-strength, and one-third-strength, containing various concentrations (0, 0.25, 0.5, and 1 mg/L) of 2-naphthoxyacetic acid (NOAA) and kinetin. The optimal medium during the multiplication phase was half-strength Murashige and Skoog medium (MS/2) supplemented with 0.5 mg/L NOAA and 0.5 mg/L kinetin (23.5 morphologically superior shoots per explant, with low vitrification rates). For the shoot elongation phase, shoots were transferred to the same proliferation medium, or to MS or MS/2 media without plant growth regulators (PGRs). Shoots elongated rapidly and showed a high rate of root formation on media supplemented with PGRs. For example, on MS/2 medium containing 1 mg/L NOAA and 1 mg/L kinetin, the average shoot length was 15.1 cm, the average number of roots per shoot was 6.2, and their average length was 3.4 cm. On PGR-free media, shoots were shorter with wider and greener leaves, and had fewer roots. The plantlets were transferred to a greenhouse for acclimation. The survival rate after 2 months was related to the medium used during the elongation phase; >90 % of shoots that were cultured on PGR-free media survived, while there was a poor survival rate of shoots that had been cultured on media containing PGRs.     

The Gut Microbiota and Developmental Programming of the Testis in Mice

Nutrients and environmental chemicals, including endocrine disruptors, have been incriminated in the current increase in male reproductive dysfunction, but the underlying mechanisms remain unknown. The gastrointestinal tract represents the largest surface area exposed to our environment and thereby plays a key role in connection with exposure of internal organs to exogenous factors. In this context the gut microbiome (all bacteria and their metabolites) have been shown to be important contributors to body physiology including metabolism, cognitive functions and immunity. Pivotal to male reproduction is a proper development of the testis, including the formation of the blood-testis barrier (BTB) that encapsulates and protects germ cells from stress induced environmental cues, e.g. pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF) mice and germ-free (GF) mice to explore whether gut microbiota and/or their metabolites can influence testis development and regulation of BTB. Lumen formation in the seminiferous tubules, which coincides with the development of the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition, perfusion experiments (Evans blue) demonstrated increased BTB permeability in these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF testis suggested that the microbiota modulated BTB permeability by regulation of cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the integrity of the BTB and normalized the levels of cell adhesion proteins. Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH) than the SPF group. In addition, the intratesticular content of testosterone was lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can modulate the permeability of the BTB and might play a role in the regulation of endocrine functions of the testis.     

Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening,synthesis, anti-proliferative,immunomodulatory, ADMET,toxicity, and molecular dynamic simulation studies

A library of modified VEGFR-2 inhibitors was designed as VEGFR-2 inhibitors. Virtual screening was conducted for the hypothetical library using in silico docking, ADMET, and toxicity studies. Four compounds exhibited high in silico affinity against VEGFR-2 and an acceptable range of the drug-likeness. These compounds were synthesised and subjected to in vitro cytotoxicity assay against two cancer cell lines besides VEGFR-2 inhibitory determination. Compound D-1 showed cytotoxic activity against HCT-116 cells almost double that of sorafenib. Compounds A-1, C-6, and D-1 showed good IC₅₀ values against VEGFR-2. Compound D-1 markedly increased the levels of caspase-8 and BAX expression and decreased the anti-apoptotic Bcl-2 level. Additionally, compound D-1 caused cell cycle arrest at pre-G1 and G2-M phases in HCT-116 cells and induced apoptosis at both early and late apoptotic stages. Compound D-1 decreased the level of TNF-α and IL6 and inhibited TNF-α and IL6. MD simulations studies were performed over 100 ns.     

Attenuation of chronic hypoxic pulmonary hypertension by simvastatin

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve multiple normal endothelial cell functions and inhibit vascular wall cell proliferation. We hypothesized that one such agent, simvastatin, would attenuate chronic hypoxic pulmonary hypertension. Male adult Sprague-Dawley rats were exposed (14 days) to normoxia (N), normoxia plus once-a-day administered simvastatin (20 mg/kg ip) (NS), hypoxia (10% inspired O2 fraction) (H), or hypoxia plus simvastatin (HS). Mean pulmonary artery pressure, measured in anesthetized, ventilated rats with an open-chest method, was reduced from 25 +/- 2 mmHg in H to 18 +/- 1 in HS (P < 0.001) but did not reach normoxic values (12 +/- 1 mmHg). Similarly, right ventricular/left ventricular plus interventricular septal weight was reduced from 0.53 +/- 0.02 in the H group to 0.36 +/- 0.02 in the HS group (P < 0.001). The increased hematocrit in H (0.65 +/- 0.02) was prevented by simvastatin treatment (0.51 +/- 0.01, P < 0.001). Hematocrit was similar in N versus NS. Alveolar vessel muscularization and medial thickening of vessels 50-200 microM in diameter induced by hypoxia were also significantly attenuated in the HS animals. Lung endothelial nitric oxide synthase (eNOS) protein expression in the HS group was less than H (P < 0.01) but was similar in N versus NS. We conclude that simvastatin treatment potently attenuates chronic hypoxic pulmonary hypertension and polycythemia in rats and inhibits vascular remodeling. Enhancement of lung eNOS expression does not appear to be involved in mediating this effect.