LD

The neem tree, Azadirachta indica, provides many useful compounds that are used as pesticides and could be applied to protect stored seeds against insects. However in addition to possible beneficial health effects, such as blood sugar lowering properties, anti-parasitic, anti-inflammatory, anti-ulcer and hepatoprotective effects, also toxic effects are described. In this study we present a review of the toxicological data from human and animal studies with oral administration of different neem-based preparations. The non-aqueous extracts appear to be the most toxic neem-based products, with an estimated safe dose (ESD) of 0.002 and 12.5 g/kg bw/day. Less toxic are the unprocessed materials seed oil and the aqueous extracts (ESD 0.26 and 0.3 mg/kg bw/day, 2 l/kg bw/day respectively). Most of the pure compounds show a relatively low toxicity (ESD azadirachtin 15 mg/kg bw/day). For all preparations, reversible effect on reproduction of both male and female mammals seem to be the most important toxic effects upon sub-acute or chronic exposure. From the available data, safety assessments for the various neem-derived preparations were made and the outcomes are compared to the ingestion of residues on food treated with neem preparations as insecticides. This leads to the conclusion that, if applied with care, use of neem derived pesticides as an insecticide should not be discouraged.

In the last two decades, networks had been changed according to the rapid changing in its requirements. The current Data Center Networks have large number of hosts (tens or thousands) with special needs of bandwidth as the cloud network and the multimedia content computing is increased. The conventional Data Center Networks (DCNs) are highlighted by the increased number of users and bandwidth requirements which in turn have many implementation limitations. The current networking devices with its control and forwarding planes coupling result in network architectures are not suitable for dynamic computing and storage needs. Software Defined networking (SDN) is introduced to change this notion of traditional networks by decoupling control and forwarding planes. So, due to the rapid increase in the number of applications, websites, storage space, and some of the network resources are being underutilized due to static routing mechanisms. To overcome these limitations, a Software Defined Network based Openflow Data Center network architecture is used to obtain better performance parameters and implementing traffic load balancing function. The load balancing distributes the traffic requests over the connected servers, to diminish network congestions, and reduce underutilization problem of servers. As a result, SDN is developed to afford more effective configuration, enhanced performance, and more flexibility to deal with huge network designs.

Mortality due to snake envenomation is not a major problem in the United States with approximately 8–12 deaths per year, but envenomation is a serious problem that can result in functional disability, loss of extremities, and a costly recovery. Physicians encounter different clinical situations with each new snakebite victim because of the geographical variations in snake venoms. The best and most acceptable form of treatment is the use of antivenom; however, it must be administered as soon as possible since it is not so effective at reducing local signs of envenomation such as necrosis. The antivenom in the United States is in short supply, expensive and may not even be the most effective for neutralizing all North American snake venoms. In this study, we tested two antivenoms. The first was a Crotalidae Polyvalent Fab fragment with Ovine origin (FabO) manufactured in London, and the second was Antivipmyn, a Mexican manufactured antivenom that is F(ab′)2 fragment produced in horse (Fab2H). The efficacy of the two antivenoms was tested with 15 different snake venoms found in North America. Three different assays were used to test the efficacy of the antivenoms, the in vivo serum protection test (ED50), antihemorrhagic and anticoagulant. The Fab2H antivenom was most effective in neutralizing the hemorrhagic activity of 78% of the hemorrhagic venoms used in this study. In the ED50 assay, the Fab2H antivenom was effective in neutralizing all venoms used in this study, while FabO neutralized all but C. m. molossus venom. However, in most cases, FabO required less antivenom than Fab2H antivenom to neutralize three LD50.

The neem tree, Azadirachta indica, provides many useful compounds that are used as pesticides and could be applied to protect stored seeds against insects. However in addition to possible beneficial health effects, such as blood sugar lowering properties, anti-parasitic, anti-inflammatory, anti-ulcer and hepatoprotective effects, also toxic effects are described. In this study we present a review of the toxicological data from human and animal studies with oral administration of different neem-based preparations. The non-aqueous extracts appear to be the most toxic neem-based products, with an estimated safe dose (ESD) of 0.002 and 12.5 g/kg bw/day. Less toxic are the unprocessed materials seed oil and the aqueous extracts (ESD 0.26 and 0.3 mg/kg bw/day, 2 l/kg bw/day respectively). Most of the pure compounds show a relatively low toxicity (ESD azadirachtin 15 mg/kg bw/day). For all preparations, reversible effect on reproduction of both male and female mammals seem to be the most important toxic effects upon sub-acute or chronic exposure. From the available data, safety assessments for the various neem-derived preparations were made and the outcomes are compared to the ingestion of residues on food treated with neem preparations as insecticides. This leads to the conclusion that, if applied with care, use of neem derived pesticides as an insecticide should not be discouraged.

This is the fifth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually taking into account the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of pyrazine derivatives as flavoring ingredients is evaluated. #

Nanotechnology, which deals with features as small as a 1 billionth of a meter, began to enter into mainstream physical sciences and engineering some 20 years ago. Recent applications of nanoscience include the use of nanoscale materials in electronics, catalysis, and biomedical research. Among these applications, strong interest has been shown to biological processes such as blood coagulation control and multimodal bioimaging, which has brought about a new and exciting research field called nanobiotechnology. Biotechnology, which itself also dates back ∼30 years, involves the manipulation of macroscopic biological systems such as cells and mice in order to understand why and how molecular level mechanisms affect specific biological functions, e.g., the role of APP (amyloid precursor protein) in Alzheimer’s disease (AD). This review aims (1) to introduce key concepts and materials from nanotechnology to a non-physical sciences community; (2) to introduce several state-of-the-art examples of current nanotechnology that were either constructed for use in biological systems or that can, in time, be utilized for biomedical research; (3) to provide recent excerpts in nanotoxicology and multifunctional nanoparticle systems (MFNPSs); and (4) to propose areas in neuroscience that may benefit from research at the interface of neurobiologically important systems and nanostructured materials.

Vipera ammodytes is the most venomous European snake, whose venom has been used as antigen for immunization of antivenom-producing animals. Same as venom of any other snake, it is a complex mixture of proteins, peptides and other compounds which biochemical and pharmacological variability has been demonstrated at interspecies and intraspecies level. In this work we demonstrated intraspecific variability between 8 venom production batches using both the conventional and the new methodology. Moreover, in contrast to the literature on different venoms' variability, for the first time we were able to select those biochemical differences that are related to and give information on the venom's toxicity and immunogenicity. We have shown that methods quantifying ammodytoxin (the most toxic compound identified so far in the Vipera ammodytes ammodytes venom) content of the venom clearly distinguish between high and low immunogenic venoms.

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to the safety evaluation of the allylalkoxybenzene derivatives methyl eugenol and estragole is critically evaluated by the FEMA Expert Panel. The hazard determination uses a mechanism-based approach in which production of the hepatotoxic sulfate conjugate of the 1 0 -hydroxy metabolite is used to interpret the pathological changes observed in different species of laboratory rodents in chronic and subchronic studies. In the risk evaluation, the effect of dose and metabolic activation on the production of the 1 0 -hydroxy metabolite in humans and laboratory animals is compared to assess the risk to humans from use of methyl eugenol and estragole as naturally occurring components of a traditional diet and as added flavouring substances. Both the qualitative and quantitative aspects of the molecular disposition of methyl eugenol and estragole and their associated toxicological sequelae have been relatively well defined from mammalian studies. Several studies have clearly established that the profiles of metabolism, metabolic activation, and covalent binding are dose dependent and that the relative importance diminishes markedly at low levels of exposure (i.e. these events are not linear with respect to dose). In particular, rodent studies show that these events are minimal probably in the dose range of 1À10 mg/ kg body weight, which is approximately 100-1000 times the anticipated human exposure to these substances. For these reasons it is concluded that present exposure to methyl eugenol and estragole resulting from consumption of food, mainly spices and added as such, 0278-6915/02/$ -see front matter # 2002 Elsevier Science Ltd. All rights reserved. P I I : S 0 2 7 8 -6 9 1 5 ( 0 2 ) 0 0 0 1 2 -1 does not pose a significant cancer risk. Nevertheless, further studies are needed to define both the nature and implications of the doseresponse curve in rats at low levels of exposure to methyl eugenol and estragole. #

In short:

New concepts and terminology were introduced in the paper: ecological tax; ecological repair of water quality. Opinion paper. Also, a review paper.
              Title: Some aspects of water filtering activity of filter-feeders.
Author(s): Ostroumov S.A.
Source: HYDROBIOLOGIA,  2005, Volume: 542,  Pages: 275-286,  DOI: 10.1007/s10750-004-1875-1;  Published: JUL 1 2005,
Text online free, in English: www.scribd.com/doc/44105992/
http://www.econf.rae.ru/article/6964
**
Key words: filter-feeders, water purification, bivalves, pollution, filtering activity,
filter-feeders, filtration, suspension feeders, benthos, ecology, aquatic, marine, water purification, bivalves, pollution, filtering activity, AFDW, ash-free dry weight, LD, liquid detergent, SD, synthetic detergent, laundry detergent, SDS, sodium dodecyl sulphate, TDTMA, tetradecyltrimethylammonium bromide, ecological tax; ecological repair, water quality, reliability, stability, functioning, ecosystem, role, habitat heterogeneity, migration of chemical elements,

**

Abbreviations: AFDW - ash-free dry weight; LD - liquid detergent; SD - synthetic detergent (laundry
detergent in the form of powder); SDS - sodium dodecyl sulphate; TDTMA
-tetradecyltrimethylammonium bromide
**
in more detail:
Abstract
On the basis of the previous publications, our new data and the existing scientific literature, we have
formulated some fundamental principles that characterize the pivotal roles of the biodiversity of filterfeeders
in ecosystems. Among those roles are: (1) the role of ecological repair of water quality, (2) the
role of contributing to reliability and stability of the functioning of the ecosystem, (3) the role of
contributing to creation of habitat heterogeneity, (4) the role of contributing to acceleration of migration
of chemical elements. It is an important feature of the biomachinery of filter-feeders that it removes from
water various particles of a very broad range of sizes. Another important principle is that the amount of
the organic matter filtered out of water is larger than the amount assimilated so that a significant part of
the removed material serves no useful function to the organism of the filter-feeder, but serves a beneficial
function to some other species and to the ecosystem as a whole. The new experiments by the author
additionally demonstrated a vulnerability of the filtration activity of filter feeders (e.g. bivalves and
rotifers) to some xenobiotics (tetradecyltrymethylammonium bromide, heavy metals and some others).
Some of new blogs with additional relevant publications:
publications authored and coathored by S.A.Ostroumov are available online free:
http://www.researchgate.net/profile/Sergei_Ostroumov/blog/5152_TextsOnlineFree;
Examples of some citations of S.A.Ostroumov's papers:
http://www.researchgate.net/profile/Sergei_Ostroumov/blog/3380_Ecology_biology_life_sciences_Bibliography ;
Book: http://www.researchgate.net/profile/Sergei_Ostroumov/blog/4528_EcotoxicologyDetergents;
FAQ (Frequently asked questions) : how to use the book and relevant papers;

https://www.academia.edu/1893508/;

Over several thousand years, the flagellated Trypanosome cruzi-causative agent of Chagas disease-developed a complex life cycle between the reduviidae vectors and its human hosts. Due to their silent and hidden location, the intracellular amastigotes are mainly responsible for the nearly 50,000 annual deaths caused by the chronic chagasic cardiomyopathy. Chagas disease is the most important parasitic disease in the Americas, though treatments have not evolved towards a more efficient pharmacotherapy that (i) eradicates the scarce amastigotes present at the indeterminate/chronic form and (ii) employs less toxic drugs than benznidazole or nifurtimox. Nano-drug delivery systems (nanoDDS) represent useful means to selectively deliver the drug to intracellular targets. However, preclinical research in Chagas must be extended in order to improve the chances of a clinical implementation. The stages involved in this process are (i) selection of the appropriate drug for a specific parasite, (ii) development of a drug-loaded nanoDDS structure that displays the adequate pharmacokinetics, biodistribution and intracellular transit and (iii) selection of the right parasite form to target and the right stage of the disease for the treatment to be started. In this review we will critically overview the few research works published in the last 20 years in the context of nanotechnology and Chagas diseases and highlight the gaps in knowledge towards the design of more efficient medicines to address this endemic.

Title: Dosis Letal Media (DL50) de algunos aceites esenciales y biocidas efectivos para el control de Ascosphaera apis en Apis mellifera L.-Median Lethal Dose (LD50) of some essential oils and biocides effective for the control of Ascosphaera apis on Apis ...

Despite the fact that we live in an era of advanced technology and innovation, infectious diseases, like malaria, continue to be one of the greatest health challenges worldwide. The main drawbacks of conventional malaria chemotherapy are the development of multiple drug resistance and the non-specific targeting to intracellular parasites, resulting in high dose requirements and subsequent intolerable toxicity. Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and the selectivity of drugs. Several nanosized delivery systems have already proved their effectiveness in animal models for the treatment and prophylaxis of malaria. A number of strategies to deliver antimalarials using nanocarriers and the mechanisms that facilitate their targeting to Plasmodium spp.-infected cells are discussed in this review. Taking into account the peculiarities of malaria parasites, the focus is placed particularly on lipid-based (e.g., liposomes, solid lipid nanoparticles and nano and microemulsions) and polymer-based nanocarriers (nanocapsules and nanospheres). This review emphasizes the main requirements for developing new nanotechnology-based carriers as a promising choice in malaria treatment, especially in the case of severe cerebral malaria.

Since its discovery, tungsten, a transition element of Group VIb of the Periodic Table of Elements, and its compounds have been considered environmentally benign. Its presence in biological and drinking water samples in Fallon, Nevada, an acute lymphocytic leukemia cluster struck community has alarmed public health, environmental and regulatory agencies. Tungsten, a metal of extraordinary properties that make it hardly substitutable, is considered an essential commodity with a wide variety of uses stretching from household necessities to highly specialized applications. This work is undertaken in order to explore aspects of environmental behavior of tungsten and its compounds. Occurrence data in terrestrial, atmospheric, aquatic and biotic systems are presented. Various aspects of environmental chemistry, fate transport across environmental interfaces and toxicology are discussed with the objective of identifying knowledge gaps and outlining directions for future research.

Aim of the study: To investigate the anticonvulsant activity of root bark extract of Carissa edulis. Materials and methods: The median lethal dose (LD 50 ) of Carissa edulis extract was determined using Lork's method (1983). The anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ)induced convulsion in mice and maximal electroshock test (MEST) in chicks, with benzodiazepine and phenytoin as standard drugs, respectively. While mechanistic studies were conducted using both flumazenil, a GABA A -benzodiazepine receptor complex site antagonist and naloxone a non-specific opioid receptor antagonist. Results: The median lethal dose (LD 50 ) of Carissa edulis was 282.8 mg/kg and over 5000 mg/kg following intraperitoneal and oral administration, respectively. Carissa edulis produced 40% and 20% protection against convulsion at 5 and 20 mg/kg, respectively, compared with 100% protection with benzodiazepine. The mean onset and percentage protection against convulsion in Carissa edulis extract-treated mice were reduced by flumazenil and naloxone. Carissa edulis exhibited dose-dependent inhibition of the convulsion induced by MEST with 20 mg/kg providing 90% protection while phenytoin (20 mg/kg) produced 100% protection. Conclusion: These results suggest that Carissa edulis possesses biologically active constituent(s) that have anticonvulsant activity which supports the ethnomedicinal claims of the use of the plant in the management of epilepsy.

A research has been conducted to synthesize compounds tend to exist in the chair (C 2h ) conformation. The capability of resorcinarene for Cr(VI) antidote was examined by orally injection method on mice groups. Based on LD 50 determination, the resorcinarene was classified as non toxic compound according to Loomis criteria. Therapeutic using quaternary ammonium-modified resorcinarene was able to reduce metal concentrations of Cr(VI) in liver, kidney, and serum in the magnitude of 78.30; 85.72, and 88.79%, respectively. The higher dose of drug administered the greater decrease in the level of heavy metal. Judging from the amount of milligrams of reduced chromium per gram of organ, kidney is the organ having highest decreasing metal concentrations.

We investigate the procedure of checking for overlap between confidence intervals or standard error intervals to draw conclusions regarding hypotheses about differences between population parameters. Mathematical expressions and algebraic manipulations are given, and ...

The current status of the GRAS evaluation program of flavoring substances operated by the Expert Panel of FEMA is discussed. The Panel maintains a rigorous rotating 10-year program of continuous review of scientific data related to the safety evaluation of flavoring substances. The Panel concluded a comprehensive review of the GRAS (GRASa) status of flavors in 1985 and began a second comprehensive review of the same substances and any recently GRAS materials in 1994. This second re-evaluation program 0278-6915/$ -see front matter Ó of chemical groups of flavor ingredients, recognized as the GRAS reaffirmation (GRASr) program, is scheduled to be completed in 2005.

Many efforts aim at solving the serious problems encountered with immunotherapy against scorpion envenoming. The most attractive approach consists in generating single-chain antibody fragments (scFv) as their pharmaco-kinetic properties should match closely those of the scorpion toxins. Although high affinity scFv reagents have been generated in the past, their production level, stability, and toxin neutralizing capacity remain disappointingly poor. In the current study, we identified one Nanobody (Nb), a single-domain antigen-binding fragment of a dromedary Heavy-chain antibody (HCAb) that recognizes specifically the Androctonus australis hector AahI toxin. This Nb has excellent production, stability and solubility characteristics. With this Nb we further manufactured a tandem linked bivalent construct and assembled a HCAb with improved antigen binding due to avidity effects. All these constructs were shown in mouse models to possess a scorpion toxin neutralization capacity that exceeds by far all previous attempts with scFv-based materials, even when used at lower doses. It is therefore clear that in the near future Nanobodies will be at the core of novel serotherapeutics as they combine multiple benefits over other reagents to treat scorpion envenomed patients.

. Toxicities of crude venoms from 49 coral snake Micrurus sp. populations, representing 15 nominal taxa, were examined in both laboratory mice and in native prey animals and compared with data gathered from two non-micrurine elapids and a crotalid, which served as outgroups. These venoms were further compared on the basis of 23 enzymatic activities. Both toxicities and enzymatic activities were analyzed with respect to natural prey preferences, as determined from stomach content analyses and literature reports. Venoms of nearly all Micrurus for which prey preferences are known, are more toxic to natural prey than to non-prey species. Except for amphisbaenians, prey are more susceptible to venoms of Micrurus that feed upon them, than to venoms of those that eat other organisms. All venoms were more toxic i.v.) i.p.) i.m. Route-specific differences in toxicity are generally greatest for preferred prey species. Cluster analyses of venom enzymatic activities resulted in five clusters, with the fish-eating M. surinamensis more distant from other Micrurus than even the crotalid, Bothrops moojeni. Ophiophagous and amphisbaenian-eating Micrurus formed two close subclusters, one allied to the outgroup species Naja naja and the other to the fossorial, ophiophagous Bungarus multicinctus. Prey preference is shown to be the most important determinant of venom composition in Micrurus. ᮊ

Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/ kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be ''generally recognized as safe'' (GRAS).

Tau phosphorylation is regulated by a balance between tau kinase and phosphatase activities. Disruption of this equilibrium was suggested to be at the origin of abnormal tau phosphorylation and thereby might contribute to tau aggregation. Thus, understanding the regulation modes of tau phosphorylation is of high interest in determining the possible causes at the origin of the formation of tau aggregates in order to elaborate protection strategies to cope with these lesions in Alzheimer's disease. Among the possible and specific interventions that reverse tau phosphorylation is the inhibition of certain tau kinases. Here, we extensively reviewed tau protein kinases, their physiological roles and regulation, their involvement in tau phosphorylation and their relevance to AD. We also reviewed the most common inhibitory compounds acting on each tau kinase.

This communication describes the general biochemical properties and some immunological characteristics of the venom from the Peruvian scorpion Hadruroides lunatus, which is the most medically relevant species in Peru. The soluble venom of this scorpion is toxic to mice, the LD 50 determined was 0.1 mg/kg and 21.55 mg/kg when the venom was injected intracranial or intraperitoneally, respectively. The soluble venom displayed proteolytic, hyaluronidasic, phospholipasic and cardiotoxic activities. High performance liquid chromatography of the soluble venom resulted in the separation of 20 fractions. Two peptides with phospholipasic activity were isolated to homogeneity and their molecular masses determined by mass spectrometry (MALDI TOF). Anti-H. lunatus venom sera were produced in rabbits. Western blotting analysis showed that most of the protein content of this venom is immunogenic. H. lunatus anti-venom displayed consistent cross-reactivity with venom antigens from the new World-scorpions Tityus serrulatus and Centruroides sculpturatus venoms; however, a weaker reactivity was observed against the venom antigens from the old World-scorpion Androctonus australis Hector.

In the last two decades, networks had been changed according to the rapid changing in its requirements. The current Data Center Networks have large number of hosts (tens or thousands) with special needs of bandwidth as the cloud network and the multimedia content computing is increased. The conventional Data Center Networks (DCNs) are highlighted by the increased number of users and bandwidth requirements which in turn have many implementation limitations. The current networking devices with its control and forwarding planes coupling result in network architectures are not suitable for dynamic computing and storage needs. Software Defined networking (SDN) is introduced to change this notion of traditional networks by decoupling control and forwarding planes. So, due to the rapid increase in the number of applications, websites, storage space, and some of the network resources are being underutilized due to static routing mechanisms. To overcome these limitations, a Software Defined Network based Openflow Data Center network architecture is used to obtain better performance parameters and implementing traffic load balancing function. The load balancing distributes the traffic requests over the connected servers, to diminish network congestions, and reduce underutilization problem of servers. As a result, SDN is developed to afford more effective configuration, enhanced performance, and more flexibility to deal with huge network designs.

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of cinnamyl derivatives as flavoring ingredients is evaluated. #

Cryptolepis buchanani Roem. & Schult. (Asclepiadaceae), a climbing tree, is used as folk medicine in southeast Asia. In Thailand, the stem of this plant is traditionally used for the treatment of inflammation, including arthritis, and muscle and joint pain. In the current study, the potential anti-inflammatory activity of a 50% ethanol extract of this plant was evaluated in a number of experimental models. For anti-acute inflammatory activity, results showed that the extract caused reduction of carrageenan-induced rat paw edema in addition to significant reduction of eicosanoid production from calcium ionophore A23187-stimulated rat peritoneal leukocytes. In a test for anti-chronic inflammatory potential utilizing the cotton thread-induced granuloma, the extract caused significant lowering of granulation tissue formation. The reduction of tumor necrosis factor-␣ (TNF-␣) release from LPS-stimulated human monocytic cell line (THP-1) was also demonstrated in cells that were pre-incubated with the extract. An additional important feature of Cryptolepis buchanani is its low toxicity, especially by oral treatment, which significantly encourages clinical trials of this extract in the human. In conclusion, the results give scientific support to the traditional use of this plant for combating inflammation. Further investigations are required to identify the active constituents responsible for the anti-inflammatory activity of Cryptolepis buchanani. Subacute and chronic toxicological studies in animals are also needed before clinical trials.

Bruchid larvae cause major losses in grain legume crops throughout the world. Some bruchid species, such as the cowpea weevil, are pests that damage stored seeds. Plants synthesize a variety of molecules, including proteinaceous proteinase inhibitors, to defend themselves against attack by insects. In this work, a trypsin inhibitor (DMTI-II) isolated from Dimorphandra mollis seeds was tested for anti-insect activity against Callosobruchus maculatus larvae. The inhibitor produced ca. 67% mortality to this bruchid when incorporated into an artificial diet at a level of 1%. The doses necessary to cause 50% mortality (LD 50 ) and to reduce weight by 50% (ED 50 ) for DMTI-II were ca. 0.50% and 0.60%, respectively. The action of DMTI-II on C. maculatus larvae may involve the inhibition of trypsin-like activity of larval midgut extracts, the absence of digestion by midgut preparations or with a mixture of pepsin and papain, and its association with a chitin column and chitinous structure in the midgut of this insect.

. Toxicities of crude venoms from 49 coral snake Micrurus sp. populations, representing 15 nominal taxa, were examined in both laboratory mice and in native prey animals and compared with data gathered from two non-micrurine elapids and a crotalid, which served as outgroups. These venoms were further compared on the basis of 23 enzymatic activities. Both toxicities and enzymatic activities were analyzed with respect to natural prey preferences, as determined from stomach content analyses and literature reports. Venoms of nearly all Micrurus for which prey preferences are known, are more toxic to natural prey than to non-prey species. Except for amphisbaenians, prey are more susceptible to venoms of Micrurus that feed upon them, than to venoms of those that eat other organisms. All venoms were more toxic i.v.) i.p.) i.m. Route-specific differences in toxicity are generally greatest for preferred prey species. Cluster analyses of venom enzymatic activities resulted in five clusters, with the fish-eating M. surinamensis more distant from other Micrurus than even the crotalid, Bothrops moojeni. Ophiophagous and amphisbaenian-eating Micrurus formed two close subclusters, one allied to the outgroup species Naja naja and the other to the fossorial, ophiophagous Bungarus multicinctus. Prey preference is shown to be the most important determinant of venom composition in Micrurus. ᮊ

Scorpion envenoming causes an intense autonomic discharge, leading to a massive release of neurotransmitters, giving rise to several pathophysiological effects. In this work we report the effects of a Bauhinia forficata aqueous extract (BfAE) upon hyperglycemia, glycogenolysis, increase of plasma catecholamines, lethality and changes in serum insulin and plasma electrolytes induced by Tityus serrulatus scorpion venom (TSV). We compare them with the effects of the regular insulin therapy. The following treatments were performed: TSV (500 g/kg, i.p.); BfAE (1 g/kg, p.o.), 24, 12 and 1 h before and immediately after TSV or saline and insulin in a single dose (1.5 IU/kg, s.c.) after TSV. BfAE reduces the fast hyperglycemia induced by TSV, but it is deprived of hypoglycemic activity. The extract also did not reduce either the intense glycogenolysis or the release of catecholamines and did not stimulate the release of endogenous insulin, although causing changes in the electrolyte plasma levels similarly to insulin. Although BfAE and insulin antagonize some effects of TSV, they should be avoided in the treatment of Tityus serrulatus envenoming, since they enhance the lethality of the venom.

Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a singl...

As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), ...

Diclofenac has recently been identified as a cause of the widespread vulture decline on the Indian subcontinent. Although the clinical signs and pathology have been described, the pathophysiology of toxicity remains unexplained. In the following study we attempt to validate the domestic fowl as a model, to allow for the further characterisation of diclofenac's mechanism of toxicity. In a lethal dose study, diclofenac was shown to have an approximate intramuscular LD 50 of 9.8 mg/kg in 18 week old layers. Signs of toxicity in the affected birds were severe depression that persisted from 24 hours post dosing to death with corresponding increased plasma uric acid concentrations. Post-mortem examinations showed signs of gout with deposits of urates (tophi) in the kidneys, liver, heart and spleen. The pharmacokinetics after both the intramuscular and oral route showed that diclofenac had a short half-life of elimination of approximately one hour, a volume of distribution of 0.09 to 0.24 L/kg and relative oral bioavailability of 50% compared to intramuscular administration. With the similarity in the clinical signs, necropsy findings, histopatological lesions and clinical pathological changes, the fowl may be used in further studies to characterise the mechanism of toxicity of diclofenac. However, due to the large difference in susceptibility of the fowl, it is not a suitable model to simulate the dose-response relationship of the vulture to the other nonsteroidal anti-inflammatory drugs.

Resumo: O artigo pretende discutir a importância da garantia do usuário no processo de planejamento e elaboração de linguagens documentárias. Assim, o trabalho de cotejamento foi realizado por meio de revisão de literatura de estudos de autores que abordam tal temática, dentro do escopo do processo classificatório, encontrado na Biblioteconomia e na Ciência da Informação. O artigo, embora concentre sua atenção na garantia do usuário, conceitua sinteticamente a garantia literária, a garantia estrutural e a garantia cultural. Discorre-se conceitualmente acerca dos Sistemas de Recuperação de Informação e dos Sistemas de Informação, das linguagens documentárias e das representações documentárias utilizadas no processo de organização da informação. Dentre as linguagens documentárias, com ênfase na representação da informação, é destacado, especificamente, o tesauro, enfocando as suas principais características no que se refere à validação de termos. Aborda os mecanismos de indexação e descrição dos documentos. Pode-se inferir que o processo de desenvolvimento dos Sistemas de Recuperação da Informação depreende, notadamente, do avanço da ciência e da tecnologia a contar de meados do século passado. No que diz respeito à construção de uma linguagem documentária, a exemplo do tesauro, conclui-se que a garantia do usuário representa um fator relevante posto que configura como a legitimação de termos que se utiliza em suas demandas de pesquisa e informação. Palavras-chave: Garantia do usuário. Organização do conhecimento. Tesauros. Representações documentárias. Indexação.

A biological assay from a pharmaceutical company is simulated with various designs and a range of parameter values. Three estimation techniquesÐFieller's method, pro®le likelihood and the bootstrapÐof ®nding con®dence intervals for the median lethal dose LD 50 are compared. Correcting for bias does not substantially improve the maximum likelihood point estimator of LD 50. The choice of the number of dose levels and sample size at each dose is seen to be critical in terms of the accuracy and precision of the estimation techniques.

In the last two decades, networks had been changed according to the rapid changing in its requirements. The current Data Center Networks have large number of hosts (tens or thousands) with special needs of bandwidth as the cloud network and the multimedia content computing is increased. The conventional Data Center Networks (DCNs) are highlighted by the increased number of users and bandwidth requirements which in turn have many implementation limitations. The current networking devices with its control and forwarding planes coupling result in network architectures are not suitable for dynamic computing and storage needs. Software Defined networking (SDN) is introduced to change this notion of traditional networks by decoupling control and forwarding planes. So, due to the rapid increase in the number of applications, websites, storage space, and some of the network resources are being underutilized due to static routing mechanisms. To overcome these limitations, a Software Defined Network based Openflow Data Center network architecture is used to obtain better performance parameters and implementing traffic load balancing function. The load balancing distributes the traffic requests over the connected servers, to diminish network congestions, and reduce underutilization problem of servers. As a result, SDN is developed to afford more effective configuration, enhanced performance, and more flexibility to deal with huge network designs.

While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC 50 , tissue residues LR 50 and oral doses LD 50 were collected from databases, each representing the largest of its kind. LC 50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action.

Ethnopharmacological relevance: Herbal preparations of Ficus bengalensis had been considered as effective, economical and safe ethnomedicines for various ailments in Indian traditional system of medicine. Aim of study: The present study was aimed to explore scientifically the antidiabetic potential of Ficus bengalensis aerial roots as its bark had already been reported to possess antidiabetic efficacy. Materials and methods: Effect of variable doses of aqueous extract of Ficus bengalensis aerial roots on blood glucose level (BGL) of normal-, sub-and mild-diabetic models have been studied and the results were compared with the reference drug Glipizide and elemental Mg and Ca intake as glycemic elements. Results: The dose of 300 mg kg −1 showed the maximum fall of 43.8 and 40.7% in BGL during FBG and glucose tolerance test (GTT) studies of normal rats, respectively. The same dose showed a marked reduction in BGL of 54.3% in sub-and 51.7% in mild-diabetic rats during GTT. The concentration of Mg (1.02%) and Ca (0.85%) identified through laser induced breakdown spectroscopy (LIBS) in the most effective dose could be responsible for this high percentage fall in BGL as they take part in glucose metabolism. Conclusion: The hypoglycemic effect in normoglycemic and antidiabetic effect in sub-and mild-diabetic models of aqueous extract of aerial roots of Ficus bengalensis are due to the presence of these glycemic elements in high concentration with respect to other elements.

Abstract: Fifty two Wistar albino rats of both sexes were used for determination of the LD50 and some toxicological studies of the active principles of Euphorbia heliscopia (sun spourge). The oral LD50 was 1211.7 mg/kg. b.wt. of crude ethyl alcohol extracts under our environmental conditions. The symptoms appear on the intoxicated animals were included increase activity and irritability, salivation, itching the nose and mouth on the cage floor, and diarrhea. The animals were tried to make tunnels under the bed and they were reluctant to stand at the cage corners. Finally the animals closed its eyes and become calm. The animals administered high dose were died after a latent period (3 hours) and some of the animals in other groups were died within 24 hours. Concerning the haematological changes, there were no significant changes of PCV, Hb concentration, RBCs count, while there were significant increase of WBCs, and monocytes. Also there were highly significant increase and decrease ...

Seventeen children with Mathematical Disability (MD), who were undergoing a remedial teaching programme in a special school were compared with an age-matched control group of seventeen children, also with MD, but studying in regular schools, on mathematical achievement over a period of one academic year. Both the groups were tested on mathematical skills once in the beginning and again at the end of one academic year. The ANCOVA results showed that the children who underwent remedial teaching showed significant improvement in pre-operational and operational domains of mathematical skills. This paper presents details of the remedial teaching method. (Samveda Remedial Teaching - Math; SRT-M) employed in the study.

Aedes aegypti adalah vektor dari penyakit demam berdarah. Menurut Depkes RI (2009), Indonesia adalah negara tertinggi yang memiliki kasus DBD di Asia Tenggara. Dalam penelitian Nugraha (2011) menyebutkan bahwa ekstrak kayu jati efektif sebagai larvasida nyamuk A. aegypti, akan tetapi belum ada studi lanjutan untuk menilai keamanannya sebagai bio-larvasida terhadap hewan coba. Tujuan dari penelitian ini adalah untuk mengetahui efek toksisitas akut ekstrak kayu jati (Tectona grandis L.f) pada mencit yang diukur secara kuantitatif dengan LD50. Jenis penelitian ini adalah eksperimen murni dengan desain post test only control group design. Sampel 30 ekor mencit Balb/c jantan yang dibagi menjadi 1 kelompok kontrol dan 4 kelompok perlakuan. Kelompok kontrol hanya mendapatkan aquades ditambahkan dengan CMC sebanyak 1ml, kelompok perlakuan I (P1) diberi sediaan uji ekstrak kayu jati dengan dosis 0,125 mg/25gBB/ml, kelompok perlakuan II (P2) dosis 1,25 mg/25gBB/ml, kelompok perlakuan III (P3)...

The horse antibodies to Naja haje (Nh) elicited in a low dose multi-site immunization protocol were investigated from binding perspective in the context of antivenom maturation. We found that, this protocol evoked the production of lethality neutralizing avid antibodies in the first round of immunization which increases over the successive immunization rounds. The changes and the relative changes in the

Ethnopharmacological relevance: In Indian traditional system of medicine, Moringa oleifera Lam. Syn. Moringa pterygosperma Gaerth (Moringaceae) is commonly used as healing herb to treat diabetes. Aim of the study: The purpose of the present study was to assess the effect of M. oleifera leaves aqueous extract therapy on glycemic control, haemoglobin, total protein, urine sugar, urine protein and body weight. Materials and methods: Variable doses of 100, 200 and 300 mg kg −1 of aqueous extract were administered orally by gavage for evaluating their hypoglycemic and antidiabetic effects on fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and post prandial glucose (PPG) of normal and streptozotocin (STZ) induced sub, mild and severely diabetic rats. Results: The dose of 200 mg kg −1 decreases blood glucose level (BGL) of normal animals by 26.7 and 29.9% during FBG and OGTT studies respectively. In sub and mild diabetic animals the same dose produced a maximum fall of 31.1 and 32.8% respectively, during OGTT. In case of severely diabetic animals FBG and PPG levels were reduced by 69.2 and 51.2% whereas, total protein, body weight and haemoglobin were increased by 11.3, 10.5 and 10.9% respectively after 21 days of treatment. Significant reduction was found in urine sugar and urine protein levels from +4 and +2 to nil and trace, respectively. Conclusion: The study validates scientifically the widely claimed use of M. oleifera as an ethnomedicine to treat diabetes mellitus.

The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Ca(v) channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Ca(v) channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Ca(v) channels, and failed to modulate LVA Ca(v) channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Ca(v) channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC(50) values were at least 1000-fold lower than in GH3 cells. L-type Ca(v) channel currents of skeletal muscle myoballs and other...