Defined plant extracts can protect human cells against combined xenobiotic effects

<p>Abstract</p> <p>Background</p> <p>Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts called Circ1, Dig1, Dig2, Sp1, and Uro1 in order to understand whether specific molecular actions took place or not.</p> <p>Methods</p> <p>Kidney and liver are major detoxification organs. We have studied embryonic kidney and hepatic human cell lines E293 and HepG2. The intoxication was induced on the one hand by a formulation of one of the most common herbicides worldwide, Roundup 450 GT+ (glyphosate and specific adjuvants), and on the other hand by a mixture of Bisphenol-A and Atrazine, all found in surface waters, feed and food. The prevention and curative effects of plant extracts were also measured on mitochondrial succinate dehydrogenase activity, on the entry of radiolabelled glyphosate (in Roundup) in cells, and on cytochromes P450 1A2 and 3A4 as well as glutathione-S-transferase.</p> <p>Results</p> <p>Clear toxicities of pollutants were observed on both cell lines at very low sub-agricultural dilutions. The prevention of such phenomena took place within 48 h with the plant extracts tested, with success rates ranging between 25-34% for the E293 intoxicated by Roundup, and surprisingly up to 71% for the HepG2. By contrast, after intoxication, no plant extract was capable of restoring E293 viability within 48 h, however, two medicinal plant combinations did restore the Bisphenol-A/Atrazine intoxicated HepG2 up to 24-28%. The analysis of underlying mechanisms revealed that plant extracts were not capable of preventing radiolabelled glyphosate from entering cells; however Dig2 did restore the CYP1A2 activity disrupted by Roundup, and had only a mild preventive effect on the CYP3A4, and no effect on the glutathione S-transferase.</p> <p>Conclusions</p> <p>Environmental pollutants have intracellular effects that can be prevented, or cured in part, by precise medicinal plant extracts in two human cell lines. This appears to be mediated at least in part by the cytochromes P450 modulation.</p

Barriers and facilitators to the implementation of doctor-nurse substitution strategies in primary care: a qualitative evidence synthesis

Item does not contain fulltextBACKGROUND: Having nurses take on tasks that are typically conducted by doctors (doctor-nurse substitution, a form of 'task-shifting') may help to address doctor shortages and reduce doctors' workload and human resource costs. A Cochrane Review of effectiveness studies suggested that nurse-led care probably leads to similar healthcare outcomes as care delivered by doctors. This finding highlights the need to explore the factors that affect the implementation of strategies to substitute doctors with nurses in primary care. In our qualitative evidence synthesis (QES), we focused on studies of nurses taking on tasks that are typically conducted by doctors working in primary care, including substituting doctors with nurses or expanding nurses' roles. OBJECTIVES: (1) To identify factors influencing implementation of interventions to substitute doctors with nurses in primary care. (2) To explore how our synthesis findings related to, and helped to explain, the findings of the Cochrane intervention review of the effectiveness of substituting doctors with nurses. (3) To identify hypotheses for subgroup analyses for future updates of the Cochrane intervention review. SEARCH METHODS: We searched CINAHL and PubMed, contacted experts in the field, scanned the reference lists of relevant studies and conducted forward citation searches for key articles in the Social Science Citation Index and Science Citation Index databases, and 'related article' searches in PubMed. SELECTION CRITERIA: We constructed a maximum variation sample (exploring variables such as country level of development, aspects of care covered and the types of participants) from studies that had collected and analysed qualitative data related to the factors influencing implementation of doctor-nurse substitution and the expansion of nurses' tasks in community or primary care worldwide. We included perspectives of doctors, nurses, patients and their families/carers, policymakers, programme managers, other health workers and any others directly involved in or affected by the substitution. We excluded studies that collected data using qualitative methods but did not analyse the data qualitatively. DATA COLLECTION AND ANALYSIS: We identified factors influencing implementation of doctor-nurse substitution strategies using a framework thematic synthesis approach. Two review authors independently assessed the methodological strengths and limitations of included studies using a modified Critical Appraisal Skills Programme (CASP) tool. We assessed confidence in the evidence for the QES findings using the GRADE-CERQual approach. We integrated our findings with the evidence from the effectiveness review of doctor-nurse substitution using a matrix model. Finally, we identified hypotheses for subgroup analyses for updates of the review of effectiveness. MAIN RESULTS: We included 66 studies (69 papers), 11 from low- or middle-income countries and 55 from high-income countries. These studies found several factors that appeared to influence the implementation of doctor-nurse substitution strategies. The following factors were based on findings that we assessed as moderate or high confidence.Patients in many studies knew little about nurses' roles and the difference between nurse-led and doctor-led care. They also had mixed views about the type of tasks that nurses should deliver. They preferred doctors when the tasks were more 'medical' but accepted nurses for preventive care and follow-ups. Doctors in most studies also preferred that nurses performed only 'non-medical' tasks. Nurses were comfortable with, and believed they were competent to deliver a wide range of tasks, but particularly emphasised tasks that were more health promotive/preventive in nature.Patients in most studies thought that nurses were more easily accessible than doctors. Doctors and nurses also saw nurse-doctor substitution and collaboration as a way of increasing people's access to care, and improving the quality and continuity of care.Nurses thought that close doctor-nurse relationships and doctor's trust in and acceptance of nurses was important for shaping their roles. But nurses working alone sometimes found it difficult to communicate with doctors.Nurses felt they had gained new skills when taking on new tasks. But nurses wanted more and better training. They thought this would increase their skills, job satisfaction and motivation, and would make them more independent.Nurses taking on doctors' tasks saw this as an opportunity to develop personally, to gain more respect and to improve the quality of care they could offer to patients. Better working conditions and financial incentives also motivated nurses to take on new tasks. Doctors valued collaborating with nurses when this reduced thei

Perceptions of nurse practitioners by emergency department doctors in Australia

BACKGROUND: The Australian Medical Association is strongly opposed to the nurse practitioner (NP) role with concerns that NPs may become doctor substitutes without the requisite training and education that the medical role demands. Despite this, NPs have been heralded by some as a potential solution to the access block, workforce shortage and increased demand affecting emergency departments (EDs). AIMS: The purpose of this study was to determine the perception of NPs by medical staff working in Australian EDs. METHODS: Semi-structured telephone interviews were conducted with closed and open-ended questions. Participants were drawn from a representative stratified sample of two city, two metropolitan and two provincial hospitals of each State/Territory. RESULTS: A total of 95 doctors from 35 EDs participated in this study including 36 Departmental Directors; 36% of participating Directors indicated having an NP on staff. Doctors were strongly opposed to the statement that NPs could replace either nurses or other prevocational doctors; 71 interviewees commented on the role of NPs in the ED. Thematic analyses revealed polarised views held by doctors. Eight major themes were identified, the most common being that there is a lack of clarity of the NP role definition, their scope of practice and differentiation from the medical role. CONCLUSION: Although ED NPs represent a highly skilled professional group their role is poorly understood by ED doctors. Opposition to the NP role is a significant barrier to the introduction of great numbers of ED NPs as a strategy to overcome the medical workforce shortage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12245-010-0214-8) contains supplementary material, which is available to authorized users

The Herbs of Life : between Tlazotéotl and Hippocratus, medicinal herbs and therapeutic practices of traditional midwives of Central Mexican Altiplano

Au Mexique et plus spécifiquement dans l’Etat du Morelos, les sages-femmes traditionnelles constituent un groupe hétérogène quant à l’origine culturelle et ethnique, aux pratiques thérapeutiques, à la personnalité, à la formation reçue, aux honoraires perçus…. Personnages à la croisée des savoirs, les sages-femmes puisent leurs connaissances dans les traditions médicales náhuatl ; elles ont également reçu une formation académique de la part de la médecine occidentale.Elles pratiquent un panachage de techniques appartenant à des traditions médicales savantes ou populaires aux systèmes de référence a priori opposés. Elles démontrent des capacités d’intégration de connaissances issues de ces différentes traditions. Leur intérêt pour les thérapies dans la mouvance actuelle des médecines dites alternatives dénote aussi leur curiosité d’esprit et la souplesse de leurs pratiques. Au plan thérapeutique, les sages-femmes occupent un espace bien spécifique avec ses caractéristiques propres dans l’accompagnement de la femme au cours du processus de la maternité,de la conception à la période puerpérale. Les bains, les massages, l’alimentation et le remède végétal constituent une de leurs principales ressources thérapeutiques; l’importance de leur pharmacopée varie d’une dizaine à une centaine de plantes. Le système thérapeutique des sages-femmes est fondé sur un invariant : le concept du chaud et du froid.In Mexico, more specifically in the state of Morelos, traditional midwives compose a heterogeneous group with regards to their cultural and ethnic origins, their therapeutic praxis, their individual personalities, their training, their fees, etc. At crossroads of knowledge sources, midwives draw their competence from Náhuatl medical traditions and benefited from an academic training from occidental medicine as well. They resort to a number of diverse techniques belonging to wise and popular medical traditions which often refer to a priori conflicting systems. Midwives from Morelos demonstrate their capacity to integrate the lore from those different traditions. Their interest towards the therapies relating to the sphere of the present so-called alternative medicines also indicates their openness and the flexibility of their praxis. From a therapeutic point of view, the midwives assume aspecific role with clear characteristics in accompanying women all along the maternity process, from conception to puerperal period. Baths, massage, nutrition and herbal remedies constitute their main therapeutical resources; the range of their pharmacopoeia varies from a dozen to about a hundredplants. The therapeutic system of the midwives is based on the invariant dichotomy of hot and cold

Dig1 protects against locomotor and biochemical dysfunctions provoked by Roundup

International audienceBACKGROUND: Plant medicinal extracts may be claimed to prevent or cure chemical intoxications. Few of these are tested for their mechanisms of actions in vivo and for their cellular impacts. In 2011, we demonstrated that hepatic cell mortality induced by environmentally realistic levels of the widely used herbicide Roundup (R) in vitro can be almost entirely prevented by plant extracts called Dig1 (D, Digeodren).METHODS: We tested the in vivo effects of D alone (1.2 ml/kg bw/d), but also prior to and during 8 days of R intoxication (at 135 mg/kg bw/d) in a total of 4 groups of 40 adult Sprague-Dawley male rats each. After treatments, horizontal and vertical locomotor activities of the animals were measured by use of actimeters. Brain, liver, kidneys, heart and testes were collected and weighted. Body weights as well as feed and water consumption were recorded. Proteins, creatinine, urea, phosphate, potassium, sodium, calcium, chloride ions, testosterone, estradiol, AST and ALT were measured in serum. In liver S9 fractions, GST, GGT, and CYP450 (1A2, 2C9, 2C19, 2D6, 3A4) were assessed.RESULTS: D did not have any physiological or biochemical observable impact alone at 2 %. Out of a total of 29 measured parameters, 8 were significantly affected by R absorption within only 8 days. On these 8 parameters, only 2 were not restored by D (GGT activity and plasmatic phosphate), 5 were totally restored (horizontal and vertical locomotor activities, CYP2D6 activity, plasmatic Na + and estradiol), and the 6th was almost restored (plasmatic K+). The specificities of the toxic effects of R and of the therapeutic effects of D treatment were thus demonstrated, both at the behavioural and biochemical levels.CONCLUSIONS: D, without any side effect observable in these conditions, presented strong preventive and therapeutic properties in vivo after a short-term intoxication by the widely used pesticide Roundup

Treatment with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine improves vascular function and lowers blood pressure in adult spontaneously hypertensive rat.

International audienceOBJECTIVE: High vascular arginase activity and subsequent reduction in vascular nitric oxide production were recently reported in animal models of hypertension. The present study investigated the effects of in-vivo arginase inhibition on blood pressure and vascular function in adult spontaneously hypertensive rats. METHODS: Ten-week-old spontaneously hypertensive rats and normotensive age-matched Wistar-Kyoto rats were treated with or without the selective arginase inhibitor N-hydroxy-nor-L-arginine for 3 weeks (10 or 40 mg/kg per day, intraperitoneally). Systolic blood pressure and cardiac rate were measured before and during treatment. Flow and pressure-dependent reactivity as well as remodeling of mesenteric arteries, acetylcholine-dependent vasodilation of aortic rings, cardiac hypertrophy, arginase activity and nitric oxide production were investigated in 13-week-old spontaneously hypertensive rats. RESULTS: In spontaneously hypertensive rats, N-hydroxy-nor-L-arginine treatment decreased arginase activity (30-40%), reduced blood pressure ( approximately 35 mmHg) and improved the reactivity of mesenteric vessels. However, vascular and cardiac remodeling was not different between treated and untreated spontaneously hypertensive rats. In Wistar-Kyoto rats, N-hydroxy-nor-L-arginine did not affect blood pressure. Finally, arginase inhibition was associated with increased nitric oxide production. Consistent with this, the response of aortic rings to acetylcholine was fully restored by N-hydroxy-nor-L-arginine, and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the effect of N-hydroxy-nor-L-arginine on flow-dependent vasodilation. CONCLUSION: Pharmacological inhibition of arginase in adult spontaneously hypertensive rats decreases blood pressure and improves the reactivity of resistance vessels. These data represent in-vivo argument in favor of selective arginase inhibition as a new therapeutic strategy against hypertension

Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines

Abstract Background Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. Methods The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. Results All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Conclusion Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.</p