Stability and enzymatic studies with omeprazole: hydroxypropyl-β-cyclodextrin

The original publication is available at www.springerlink.com. A publicação original está disponível em www.springerlink.comOmeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-b-cyclodextrin (HPbCD). Stability of OME, its physical mixture (PM) with HPbCD and OME:HPbCD inclusion complex was assessed during 60 days. The inclusion complexes were prepared by kneading and freezedrying techniques and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). A molecular modelling was also held to predict the most probable tridimensional conformation of inclusion complex OME:HPbCD. The inhibitory activity of free and complexed OME on selected enzymes, namely, papain (protease model of the proton pump) and acetylcholinesterase (enzyme present in cholinergic neurons and also involved in Alzheimer’s disease) was compared. The results obtained show that HPbCD do not protect against OME degradation, in any prepared powder, in the presence of light, heat and humidity. This may indicate that the reactive group of OME is not included in the HPbCD cavity. This fact is supported by molecular modelling data, which demonstrated that 2-pyridylmethyl group of OME is not included into the cyclodextrin cavity. In relation to enzymatic assays it was observed that free OME and OME in the binary systems showed identical inhibitory activity on papain and acethylcolinesterase, concluding that HPbCD do not affect OME activity on these two enzymes

Transcriptional responses underlying the hormetic and detrimental effects of the plant secondary metabolite gossypol on the generalist herbivore Helicoverpa armigera

<p>Abstract</p> <p>Background</p> <p>Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds which are otherwise detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some plants in the family Malvaceae. We investigated the developmental effect of gossypol in the cotton bollworm, <it>Helicoverpa armigera</it>, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses.</p> <p>Results</p> <p>Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three concentrations (0%, 0.016% and 0.16%) were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment. Hormesis could be observed at the transcript level, since at the low gossypol dose, genes involved in energy acquisition such as β-fructofuranosidases were up-regulated in the gut, and genes involved in cell adhesion were down-regulated in the body. Genes with products predicted to be integral to the membrane or associated with the proteasome core complex were significantly affected by the detrimental dose treatment in the body. Oxidoreductase activity-related genes were observed to be significantly altered in both tissues at the highest gossypol dose.</p> <p>Conclusions</p> <p>This study represents the first transcriptional profiling approach investigating the effects of different concentrations of gossypol in a lepidopteran species. <it>H. armigera</it>'s transcriptional response to gossypol feeding is tissue- and dose-dependent and involves diverse detoxifying mechanisms not only to alleviate direct effects of gossypol but also indirect damage such as pH disturbance and oxygen radical formation. Genes discovered through this transcriptional approach may be additional candidates for understanding gossypol detoxification and coping with gossypol-induced stress. In a generalist herbivore that has evolved transcriptionally-regulated responses to a variety of different plant compounds, hormesis may be due to a lower induction threshold of growth-promoting, stress-coping responses and a higher induction threshold of detoxification pathways that are costly and cause collateral damage to the cell.</p

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

<p>Abstract</p> <p>Background</p> <p>N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.</p> <p>Results</p> <p>By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.</p> <p>Conclusion</p> <p>These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.</p

Agroecology and Health: Lessons from Indigenous Populations.

Purpose of reviewThe article aims to systematize and disseminate the main contributions of indigenous ancestral wisdom in the agroecological production of food, especially in Latin America. For this purpose, it is necessary to ask whether such knowledge can be accepted by academia research groups and international forums as a valid alternative that could contribute to overcome the world's nutritional problems.Recent findingsAlthough no new findings are being made, the validity of ancestral knowledge and agroecology is recognized by scientific research, and by international forums organized by agencies of the United Nations. These recommend that governments should implement them in their policies of development, and in the allocation of funds to support these initiatives. Agroecology and ancestral knowledge are being adopted by a growing number of organizations, indigenous peoples and social groups in various parts of the world, as development alternatives that respond to local needs and worldviews. Its productive potential is progressively being recognized at an international level as a model that contributes to improve the condition of people regarding nutritional food

Akutna oralna toksičnost organofosfornih insekticida i inhibicija kolinesteraza u pilića

Acute toxic effects of three commonly used insecticidal preparations of the organophosphates chlorpyrifos, diazinon, and dichlorvos were examined in mixed breed broiler chicks, and cholinesterase activity in plasma and brain were measured. The acute (24 h) oral median lethal doses (LD50) of chlorpyrifos, diazinon, and dichlorvos were 10.79 mg kg-1, 6.32 mg kg-1, and 6.30 mg kg-1, respectively, as determined by the up-and-down method in chicks. Signs of cholinergic toxicosis in the chicks appeared within two hours after dosing, and they included salivation, lacrimation, gasping, frequent defecation, drooping of wings, tremors, convulsions, and recumbency before death. Halving the oral LD50 of chlorpyrifos (5 mg kg-1), diazinon (3 mg kg-1), and dichlorvos (3 mg kg-1) caused immobility and wing drooping, but not the clinical signs of cholinergic toxicity. However, at full LD50 doses of these insecticides, chicks showed clinical signs of cholinergic toxicity similar to those seen in the LD50 experiments. Two out of six chicks died within two hours after treatment with LD50 doses of chlorpyrifos and dichlorvos, whereas LD50 dosing with diazinon caused death in three out of six chicks. Compared to control values, the insecticides reduced plasma and whole brain cholinesterase activities by 29 % to 84 % and 18 % to 77 %, respectively, depending on the dose. The decrease in plasma cholinesterase correlated well (r = 0.82) with that of the brain. These data suggest that organophosphate insecticides administered orally at LD50 doses induce clinical signs of cholinergic poisoning and concurrently reduce brain and plasma cholinesterase activities in chicks.Ispitano je akutno toksično djelovanje triju često rabljenih organofosfornih insekticida klorpirifosa, diazinona i diklorvosa u brojlera te je izmjerena aktivnost kolinesteraza u njihovoj plazmi i mozgu. Srednja letalna doza LD50 klorpirifosa iznosila je 10,79 mg kg-1, diazinona 6,32 mg kg-1 te diklorvosa 6,30 mg kg-1. Prvi su se znakovi kolinergičkoga sindroma u pilića javili unutar dva sata od oralne primjene, a obuhvaćali su slinjenje, suženje, teško disanje, učestalu defekaciju, obješena krila, drhtavicu, grčenje i nesposobnost stajanja uoči smrti. Oralna primjena polovice srednje letalne doze insekticida klorpirifosa (5 mg kg-1), diazinona (3 mg kg-1) i diklorvosa (3 mg kg-1) dovela je do nepokretnosti i obješenih krila, ali bez kliničkih znakova kolinergičke toksičnosti koji su uočeni kod pokusa radi utvrđivanja srednje letalne doze (LD50). Međutim, doze ovih insekticida koje su odgovarale LD50, dovele su do kliničkih znakova kolinergičke toksičnosti sličnih onima zamijećenim kod utvrđivanja LD50. Dva od šest pilića uginula su unutar dva sata od primjene bilo klorpirifosa bilo diklorvosa u dozama koje su odgovarale LD50, dok je diazinon u odgovarajućoj srednjoj letalnoj dozi uzrokovao smrt triju od šest pilića. U odnosu na kontrolne vrijednosti, insekticidi su doveli do smanjenja aktivnosti kolinesteraze koja je ovisila o dozi, a kretala se od 29 % do 84 % u plazmi te od 18 % do 77 % u mozgu. Pad aktivnosti kolinesteraze u plazmi dobro je korelirao s njezinim padom u mozgu (r=0,82). Ovi podaci upućuju na to da oralna primjena organofosfornih insekticida u dozama koje odgovaraju srednjoj letalnoj dozi dovode do znakova kolinergičkoga trovanja u pilića te do istodobnoga pada aktivnosti kolinesteraza u mozgu i plazmi

Gut microbiota composition in relation to intake of added sugar, sugar-sweetened beverages and artificially sweetened beverages in the Malmö Offspring Study

Purpose It has been suggested that a high intake of sugar or sweeteners may result in an unfavorable microbiota composition; however, evidence is lacking. Hence, in this exploratory epidemiological study, we aim to examine if intake of added sugar, sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) associate with the gut microbiota composition. Methods Participants (18–70 years) in the Malmö Offspring Study have provided blood, urine, and fecal samples and completed both web-based 4 day food records and short food frequency questionnaires. The gut microbiota was assessed by 16S rRNA sequencing, processed in QIIME and matched to Greengenes (v.13.8), giving 64 included genera after filtering. Intake of added sugar (n = 1371) (also supported by the overnight urinary sugar biomarker in a subgroup n = 577), SSBs (n = 1086) and ASBs (n = 1085) were examined as exposures in negative binomial regressions. Results Various genera nominally associated with intake of added sugar, SSBs, and ASBs. Only the negative association between SSB intake and Lachnobacterium remained significant after multiple testing correction. A positive association between SSB intake and the Firmicutes:Bacteroidetes ratio was also observed. Conclusion In this wide population, the cross-sectional associations between added sugar and sweet beverage intake and the gut microbiota are modest, but the results suggest that SSB intake is associated negatively with the genus Lachnobacterium and positively with the Firmicutes:Bacteroidetes ratio. Larger studies, preferably using metagenomic sequencing, are needed to further evaluate if a link exists between intake of sugars and sweeteners and the human gut microbiota

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Veterans of Operation Desert Storm/Desert Shield - the 1991 Gulf War (GW) - are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25-32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants

Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity