Opiate receptor blockade in man reduces 2-deoxy-d-glucose-induced food intake but not hunger,thirst, and hypothermia

Opioid peptides may act as neuromodulators in the central nervous system to conserve energy stores and water in mammals. To examine this hypothesis in man, the effect of opiate receptor blockade with naloxone on the hunger, thirst, and hypothermic response to 2-deoxy-D-glucose-induced glucoprivic stress was assessed. Opiate receptor blockade decreased stress-induced food intake but did not reduce marked increases in hunger produced by glucoprivation. Naloxone infusions did not change the hypercortisolemic, polydipsic, hypothermic, and thermogenic response to 2-deoxy-D-glucose. While these results do not suggest a major role for a β-endorphin modulation of stress-induced hunger, hypothermia and water conservation, the reduction of food intake could be due to augmented satiety, perhaps associated with retardation of gastric emptying during opiate receptor blockade.     

Insecticidal activity of substituted phenyl N-methylcarbamates

The insecticidal and the acaricidal activities of a number of substituted phenyl N-methylcarbamates have been determined on the housefly (Musca domestica), the black bean aphid (Aphis fabae), the Colorado potato beetle (Leptinotarsa decemlineata), the cabbage worm (Pieris brassicae) and the carmine spider mite (Tetranychus cinnabarinus).It is demonstrated that the thesis of Kolbezen, Metcalf & Fukuto (1954), Metcalf, Fukuto & Winton (1962) and Kohn, Ospenson & Moore (1965), that the meta-isomers of alkylphenyl N-methylcarbamates are the most active, has to be restricted to some insect groups (e.g. flies and caterpillars). In the case of the Colorado potato beetle the o- and m-isomers were equally active; for aphids the o-isomer was the most toxic one.This fact as well as the different responses of the test insects if the compounds are further alkylated indicate that various carbamates exhibit more or less selective activities. Most striking was the high level of activity in the new group of p-dimethylaminomethylphenyl N-methylcarbamates on most of the insects, in combination with a complete lack of toxicity to houseflies.As previously pointed out by Kolbezen et al. (1954) and Metcalf et al. (1962), it was found that lengthening of the N-methyl group or N,N-dialkylation resulted in loss of insecticidal activity.The most active dimethylaminophenyl compounds were those with a p-dimethylamino group in combination with alkyl substituents in the 2,5- and 3,5-positions. Several p-dimethylaminomethylphenyl N-methylcarbamates with two or three alkyl substituents (except the 2,6-combination) proved to be highly active, except on flies, to which they were virtually nontoxic. Greatest broad-spectrum activity was shown by 2,3-dimethyl-4-dimethylaminomethylphenyl N-methylcarbamate. It is demonstrated that by introducing a p-dimethylamino- or a p-dimethylaminomethyl group in alkylphenyl N-methylcarbamates a considerable gain in anticholinesterase and insecticidal activity is obtained.

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Résumé p L'activité insecticide et acaricide de plusieurs N-méthylcarbamates de phényle substitués a été examinée sur la mouche domestique (Musca domestica), le puceron noir (Aphis fabae), le doryphore (Leptinotarsa decemlineata), la chenille de la piéride du chou (Pieris brassicae) et l'araignée rouge des serres (Tetranychus cinnabarinus). Les N-méthylcarbamates de phényle monosubstitués ne présentent qu'une faible activité acaricide. Les substances avec des substitutions en position méta ou ortho montrent une meilleure activité insecticide que celles avec la substitution en position para. Pour les mouches domestiques l'alcoylation en position méta se trouve donner les composés les plus actifs; pour les pucerons l'alcoylation en position ortho était la plus efficace et pour les doryphores les combinaisons o- et m-étaient d'une activité égale. Les isomères ortho des dérivés alcoxylés étaient plus efficaces. En cas de substitution par un groupe diméthylamino il n'y a pas de différence importante quant à l'activité insecticide entre les positions ortho ou méta. En général il en est de même pour les substitutions par diméthylaminométhyle, bien que le m-isomère soit le plus efficace sur les chenilles.L'introduction d'un deuxième groupe alcoyle dans un N-méthylcarbamate de o- ou m-isopropylphényle change le spectre d'action. Un groupe 5-méthyle diminue beaucoup l'activité de l'o-isomère. Un groupe 5-isopropyle diminue l'activité sur les pucerons, mais pas sur les mouches. Quand un groupe 5-méthyle ou 5-isopropyle est introduit dans un N-méthylcarbamate de m-isopropyl-phényle l'activité est généralement augmentée. L'introduction d'un groupe 6-méthyle diminue toutefois l'activité sur les mouches, les pucerons et les chenilles, mais pas sur les Coléoptères et les araignées rouges.Les N-méthylcarbamates de phényle s'avèrent posséder une meilleure activité que les combinaisons N,N-diméthylcarbamates correspondantes. Une prolongation du groupe N-alcoyle diminue également l'activité.Les dérivés de N-méthylcarbamates de 2-diméthylamino-phényle ont une plus grande activité que les isomères méta correspondants. On trouve toutefois la meilleure activité dans les N-méthylcarbamates de 4-diméthylamino-phényle alcoylés. Tout groupe alcoyle, à condition d'être introduit en position 2-, 3-, ou 5-augmente l'activité insecticide. Les composés métasubstitués semblent encore un peu plus actifs que les dérivés d'o-alcoyle. La grande activité sur les pucerons contraste nettement avec la faible activité sur les mouches et les araignées rouges. Le seul dérivé présentant une bonne activité sur les araignées rouges est le N-méthylcarbamate de 3-isopropyl-4-diméthylamino-5-méthylphényle.Les N-méthylcarbamates de p-diméthylaminométhyl-phényle alcoylés présentent également une forte action insecticide, sauf sur les mouches. Le N-méthylcarbamate de 2, 3-diméthyl-4-diméthylaminométhyl-phényle présente la plus grande activité et le plus large spectre d'action.A partir des N-méthylcarbamates d'alcoylphényle l'introduction d'un groupe p-diméthylamino ou p-diméthylamino-méthyle augmente considérablement l'activité anticholinestérasique aussi bien que l'activité insecticide.

     

Biocides formulation of essential oils having antimicrobial activity

Essential oils of fennel, peppermint, caraway, eucalyptus, geranium and lemon were tested for their antimicrobial activities against some plant pathogenic micro-organisms (Fusarium oxysporum, Alternaria alternate, Penicilium italicum Penicilium digitatum and Botyritus cinerea). Essential oils of fennel, peppermint, caraway were selected as an active ingredient for the formulation of biocides due to their efficiency in controlling the tested micro-organisms. Successful emulsifiable concentrates (biocides) were prepared from these oils using different emulsifiers (Emulgator B.L.M. Tween20 and Tween80) and different fixed oils (sesame, olive, cotton and soybean oils). Physico-chemical properties of the formulated biocide (spontaneous emulsification, emulsion stability test, cold stability and heat stability tests as well as viscosity, surface tension and pH) were measured. The prepared biocides were ready to be tested for application in a future work as a safe pesticide against different pathogens.     

Neural networks in intestinal immunoregulation

Key physiological functions of the intestine are governed by nerves and neurotransmitters. This complex control relies on two neuronal systems: an extrinsic innervation supplied by the two branches of the autonomic nervous system and an intrinsic innervation provided by the enteric nervous system. As a result of constant exposure to commensal and pathogenic microflora, the intestine developed a tightly regulated immune system. In this review, we cover the current knowledge on the interactions between the gut innervation and the intestinal immune system. The relations between extrinsic and intrinsic neuronal inputs are highlighted with regards to the intestinal immune response. Moreover, we discuss the latest findings on mechanisms underlying inflammatory neural reflexes and examine their relevance in the context of the intestinal inflammation. Finally, we discuss some of the recent data on the identification of the gut microbiota as an emerging player influencing the brain function.     

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

Micelle‐enhanced spectrofluorimetric method for determination of sitagliptin and identification of potential alkaline degradation products using LC‐MS

A novel, quick, simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of sitagliptin (SG) in its pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behavior of sitagliptin in an SDS micellar system. In an aqueous solution of phosphate buffer pH 4.0, the fluorescence intensity of SG in the presence of SDS was greatly enhanced, by 200%, i.e. twofold enhancement. The fluorescence intensity of SG was measured at 300 nm after excitation at 270 nm. The method showed good linearity in the range 0.03–10.0 µg/mL with a good correlation coefficient (r = 0.9998). The limits of detection and quantitation values were 5.31 and 16.1 ng/mL, respectively. The proposed method was successfully applied to the analysis of SG in its single and co‐formulated commercial tablets; the results were in good agreement with those obtained using a reference method. Application of the proposed method was extended to stability studies of SG after exposure to different forced degradation conditions according to the ICH guidelines, such as acidic, alkaline, thermal, photo‐ and oxidative stress. The chemical structure of certain potential degradation products (DPs) were investigated using LC‐MS. Copyright © 2013 John Wiley & Sons, Ltd.     

Lung tissue extracellular matrix-derived hydrogels protect against radiation-induced lung injury by suppressing epithelial–mesenchymal transition

This study aimed to examine whether lung tissue extracellular matrix (ECM) hydrogels have protective effects on radiation-induced lung injury (RILI). The cytocompatibility and histocompatibility were tested for the obtained ECM-derived hydrogel. Sprague–Dawley rats were randomly divided into three groups (n = 18): control group (control); rats receiving irradiation and intratracheal injection of normal saline (IR + NS); and rats receiving irradiation and intratracheal injection of lung ECM-derived hydrogel (IR + ECM). The wet/dry weight ratio was used to evaluate the congestion and edema of the lungs. Histopathological analysis of lung tissues was performed using hemotoxylin and eosin staining and Masson's trichrome staining. Immunohistochemical staining and western blot analyses were carried out to determine the expression of epithelial–mesenchymal transition (EMT)-related proteins in lung tissues (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin). In addition, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6), hydroxyproline, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were also evaluated. The ECM-derived hydrogels had good cytocompatibility and histocompatibility. ECM-derived hydrogel treatment improved lung histopathology injury and pulmonary edema. Higher expression of E-cadherin and lower expression of vimentin and α-SMA were found in the IR + ECM group compared with those in the IR + NS group. Hydroxyproline levels were reduced by ECM-derived hydrogel treatment compared with those in the IR + NS group. Obvious increases of TNF-α, IL-6, and TGF-β1 were identified following irradiation. Marked reductions in MDA content and increases in SOD were induced by ECM-derived hydrogel treatment in rats after radiation. ECM-derived hydrogels were shown to protect against RILI, potentially by reducing EMT, inflammation, and oxidative damage.