New high-performance liquid chromatography-dad method for analytical determination of arbutin and hydroquinone in rat plasma

Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances

An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology

© 2017 Elsevier B.V. All rights reserved.Ethnopharmacological relevance: The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Materials and methods: Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including ‘Diabetes’ ‘Gabon’ ‘Toxicity’ ‘Constituents’ ‘hyperglycaemia’ were used. Results: A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. Conclusion: An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.Peer reviewedFinal Accepted Versio

Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis.

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2-78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0-88.0%), unsteady gait (58%; 48.2-67.8%), and weakness (43%; 33.1-52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9-83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70.7%; 60.7-80.8%), homocysteine >15 µmol/L (90.3%; 79.3-100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4-100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment

Toxicological Study Employing Repeated Doses of Garcinielliptone FC, a Polyisoprenylated-Benzophenone Isolated from Seed of Platonia Insignis Mart

The major constituent from the hexane extract of the seeds of P. insignis is GFC (garcinielliptone FC). Doses of 25, 50and 75 mg/kg of GFC were aseptically suspended in 0.05% Tween 80 dissolved in 0.9% saline (vehicle) and orally administered for30, 90 and 120 consecutive days to adult Swiss mice. In this work, the repeated oral administration, in animals of both sexes,demonstrates that this compound is not able to induce mortality and/or behavioral changes in adult mice. In addition, body weightgain, feed intake and disposal of excreta were not altered by the administration of this compound with repeated doses. Furthermore,no differences in weight and macroscopic structure of the brain, liver, kidney, lung, heart and spleen between groups of male andfemale adult mice were observed after treatment. During the periods of treatment, GFC produced no significant changes onhaematological and biochemical parameters in male and female mice treated with all doses used. The aim of this study was toinvestigate the toxicological potential of GFC through behavioral, hematological, biochemical and morphological parameters inanimals in order to ensure the safe use of Platonia insignis in folk medicine.Fil: Silva, Ana P.. Federal University of Piauí; BrasilFil: Filho, José Carlos C. L. S.. North Union of Parana; BrasilFil: da Costa Júnior, Joaquim S.. Federal Institute of Piauí; BrasilFil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Falcão Ferraz, Alexandre de B.. Lutheran University of Brazil; BrasilFil: David, Jorge M.. Institute Of Chemistry, Federal University Of Bahia; Brasil. Universidade Federal da Bahia; BrasilFil: Freitas, Rivelilson M.. Federal University of Bahia; Brasi

Rapid healing of a patient with dramatic subacute combined degeneration of spinal cord: a case report

Background: Prevalence of cobalamin deficiency is high especially in older patients and an immediate therapy start is necessary to prevent irreversible neurological damages. Unfortunately, the diagnosis of cobalamin deficiency is difficult and at present, there is no consensus for diagnosis of this deficiency. Therefore, we aim to elucidate a meaningful diagnostic pathway by a case report with an initially misleading medical history. Case presentation: A 57 year-old Caucasian man suffering from dramatic myelosis of the cervical posterior columns. Apart from associated neurological symptoms (tactile hypaesthesia, reduced vibration sensation, loss of stereognosis and of two-point-discrimination) there were no further complaints; especially no gastrointestinal, haematological or psychiatric disorders were provable. Cobalamin (vitamin B12) serum level was normal. The diagnosis of subacute combined degeneration of spinal cord was confirmed by an elevated methylmalonic acid, and hyperhomocysteinemia. Cobalamin deficiency was caused by asymptomatic chronic atrophic inflammation of the stomach with a lack of intrinsic factor producing gland cells. This was revealed by increased gastrin and parietal cell antibodies and finally confirmed by gastroscopy. Parenteral substitution of cobalamin rapidly initiated regeneration. Conclusions: This case demonstrates that normal cobalamin serum levels do not rule out a cobalamin deficiency. In contrast, path-breaking results can be achieved by determining homocysteine, holotranscobalamin, and methylmalonic acid

Effects of oral administration of a fuel cell product water to Macaca mulatta Final report, Jan. - Feb. 1965

Fuel cell product water given to monkeys as sole source of fluid intake for 14-day perio

Toxicity studies of Coolanol 15 Final report, Jan. - Sep. 1965

Toxicity studies of synthetic fluid coolant for manned spacecraft heat transfer system

Chronic toxicity of inhaled thymol in lungs and respiratory tracts in mouse model.

Epinephrine HFA (Primatene® Mist) is a newly formulated asthma metered dose inhaler developed to replace the previous Primatene® Mist CFC. The formulation of Epinephrine HFA contains thymol, a substance recognized to be safe by the FDA. Although the content of thymol contained in Epinephrine HFA is much lower compared to many common foods and medications available, there are no known nonclinical data about the chronic toxicity of thymol through inhalation. Two sequential 6-month studies of identical design were conducted to assess the chronic toxicity of inhaled thymol in mice. Four treatment groups, (a) Air; (b) vehicle control; (c) Article-1 (thymol 0.1%); and (d) Article-2 (thymol 0.5%) were assessed in 128 mice for 26 weeks. The mice were sacrificed at the end of the treatment period and a histopathologic evaluation was performed with respect to lungs, bronchial lymph nodes, nasal passages/nasopharynx, and trachea. Forty-five pathologic assessment parameters (PAPs) were evaluated. In total, 5591 data points from 487 mouse organs were assessed. Chronic toxicity index was calculated for 16 PAPs that had multiple histopathologic abnormal observations. The t tests were conducted for these 16 PAPs (Articles-1 and 2 versus Air and vehicle control, respectively), and all P-values were greater than .05 indicating no significant differences between all treatment groups. An evaluation was also conducted for 25 PAPs that had only a very small number of pathologic abnormalities. No significant differences for chronic toxicity were found when comparing mice under long-term repeated exposure of high doses of inhaled thymol and mice that inhaled no thymol

Scientific Opinion on Flavouring Group Evaluation 302 (FGE.302): N-(2-methylcyclohexyl)-2,3,4,5,6-pentafluoro-benzamide from Chemical Group 30

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