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Dendrocnide moroides (also known as gympie-gympie, mulberrylike stinging tree, or stinger) is arguably the most brutal of stinging plants, even leading to death in dogs, horses, and humans in rare cases. They can be recognized as shrubs with heart-shaped, serrated, dark green leaves that are covered in what appears to be soft downy fur with red to dark purple raspberries growing on long stems. After contact, there is immediate piloerection and local swelling, which may disappear after 1 hour or last as long as 24 hours, but the subjective pain, pruritus, and burning can persist for months. One can only treat conservatively with symptom management, and the most successful method of removing plant hair is hair removal wax strips, which are considered an essential component of a first aid kit where D moroides is found.

Robotic harvesting research has seen significant achievements in the past decade, with breakthroughs being made in machine vision, robot manipulation, autonomous navigation and mapping. However, the missing capability of obstacle handling during the grasping process has severely reduced harvest success rate and limited the overall performance of robotic harvesting. This work focuses on leaf interference caused slip detection and handling, where solutions to robotic grasping in an unstructured environment are proposed. Through analysis of the motion and force of fruit grasping under leaf interference, the connection between object slip caused by leaf interference and inadequate harvest performance is identified for the first time in the literature. A learning-based perception and manipulation method is proposed to detect slip that causes problematic grasps of objects, allowing the robot to implement timely reaction. Our results indicate that the proposed algorithm detects grasp slip with an accuracy of 94%. The proposed sensing-based manipulation demonstrated great potential in robotic fruit harvesting, and could be extended to other pick-place applications.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 33 Citrus flower- and leaf-derived ingredients, which are most frequently reported to function in cosmetics as fragrances and/or skin-conditioning agents. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. With Citrus flower- and leaf-derived ingredients, the Panel was concerned about the presence of the hydroperoxides of limonene and linalool in cosmetics. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that these ingredients are safe in the present practices of use and concentration when formulated to be non-irritating and non-sensitizing.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment and prevention of inflammation with the increase in number of side effects. Traditional plants have been used to treat inflammation owing to lesser adverse responses. Croton bonplandianus being an anti-inflammatory plant is extensively utilized all over the world. The methanolic and aqueous leaves extracts of Croton bonplandianus were exposed to anti-inflammatory activity in the carrageenan induced paw edema against standard diclofenac sodium, followed by the histopathlogical examination. The highest dose of methanolic extract were shown significant anti-inflammatory action having a significant P-value (P<0.05-0.001) compared with the diclofenac sodium (P<0.01-0.001) and aqueous extracts (P<0.5-0.01). The histopathological examination illustrated the vasodialation with reduction in the intensity of edema, neutrophils infiltration and other inflammatory cells. C. bonplandianus being a reactive oxygen species scavenger, responsible to exert an excellent anti-inflammatory activity. The present study confirmed the anti-inflammatory potential of drug extracts and authors recommended its utilization in the treatment of pain, inflammation and relevant diseases in future. However, phytochemical screening is to be required for the complete evaluation of active chemical constituent (s).

Materials and Methods: Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies., Results: Acute toxicity study showed that the oral LD 50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys., Conclusion: Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species " Haloxylon scoparium pomel" in subchronic treatments., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Loubna Kharchoufa et al.)

Objectives: Annona muricata, also known as graviola, soursop and guanabana, has been widely utilised for the treatment of a range of cancers. The mechanism of action and the efficacy of A. muricata and its constituents in the treatment of cancer have been comprehensively reviewed. The aim of this systematic review was to summarise the available literature that reports on factors related to the safety and tolerability of A. muricata leaf extract and its acetogenins., Methods: In-vitro, preclinical animal studies and human studies of any design written in any language were included. Studies that evaluated A. muricata leaf extract and its constituents were searched through the databases Pubmed, Medline and Embase from inception to April 2019. The elaborated item 4 of Consolidated Standards of Reporting Trials statement and Animals in Research: Reporting In vivo Experiments guidelines were used to evaluate the quality of the studies., Key Findings: The results suggest that A. muricata and its constituents have hepatoprotective, neurotoxic, antinociceptive, anti-ulcerative and chemopreventive effects. The dose and duration used in animal studies demonstrating toxicity may not directly translate into the effects in humans. Studies included in this review were judged to be of medium to high quality., Conclusions: The overall outcome of the current review suggests that A. muricata has a favourable safety and tolerability profile. Future studies investigating its use in people diagnosed with a range of cancers are warranted., (© 2019 Royal Pharmaceutical Society.)

Background and Objective: Khat is a plant that contains the alkaloids cathine and cathinone which have some amphetamine-like properties. It is cultivated and it's leaves chewed for their euphoric effect. This study intended to elucidate the effect of khat chewing on blood coagulation by using the International Normalized Ratio (INR) value as a calculable benchmark., Materials and Methods: In this cohort study, 146 patients with Mechanical Heart Valves (MHV) were assessed for two consecutive visits at one-month intervals. For each visit, the date of surgery, the patient's compliance, the dose of warfarin and the INR reading were assessed by the researcher., Results: Out of 146 patients with MHV, the mean age was 33.72±12.43 years (range, 14-65 years); 82 (56.2%) were female and 64 (43.8%) were male. The results revealed that the mean of absolute INR readings was lower in khat-chewers than non-chewers by average 0.2 on the first and second visits (p = 0.038 and 0.002, respectively)., Conclusion: Khat chewing has a significant coagulant effect. There was a significant decrease in the value of INR for khat chewers patients with MHV when compared to non-khat chewers.

Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in mortality. To the best of our knowledge, we identified the first case of K. ohmeri keratitis following an injury with vegetative material. A 57-year-old woman with underlying, poorly controlled diabetes mellitus was gardening when a tree leaf accidentally poked her in the eye. Two weeks later, the patient presented with right eye pain, redness and progressive blurring of vision due to a traumatised right cornea. Slit-lamp examination showed a small inferior paracentral corneal stromal infiltrate with overlying epithelial defect. A corneal scraping sample yielded K. ohmeri from Analytical Profile Index (API) 20C yeast identification system. She was treated with intensive topical amphotericin B and fluconazole. After 6 weeks of treatment, the keratitis resolved with faint scar tissue, and her visual acuity improved., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The harmful effects of khat chewing on the oral mucosa membrane are still uncertain. Verruca vulgaris (common warts) is a benign lesion of skin and mucous membranes and can be caused by human papillomavirus. The lesions are typically self-limited but may vary in size and number. The occurrence on the floor of mouth is extremely rare. To the best of our knowledge, there are few number of oral lesions reported in connection with khat users. This case report shows that the chronic khat chewing has contributed to the development of verruca vulgaris warts that were confined to the chewing side of the mouth. A rare case of verruca vulgaris of the floor of mouth occurring in a 27-year-old Yamani male is presented with a discussion on etiopathogenesis and the treatment methods. Verruca vulgaris must be remembered in the differential diagnosis of the floor of mouth lesions, and surgical treatment may provide satisfactory outcomes., Competing Interests: None

A 2-year-old child was accompanied by his parents to the pediatric emergency room for refusal to eat, trismus and generalized contractures four days after the application of a traditional topical treatment (Cassava leaves) on lesions of a severe thermal burn. A temperature of 38̊C, a heart rate of 114 beats/min, and a blood pressure of 90/60 mm Hg were recorded. The tetanus vaccination was not up to date. The diagnosis of tetanus was immediately suggested. Antitetanus serum (immunoglobulin), an antibiotic (amoxicillin and clavulanic acid), and a myorelaxant (benzodiazepine) were administered. Local treatments were also performed. The child died within 24 hours.

What Is Known and Objective: Moringa oleifera (MO) Lam (Moringaceae) is commonly used as food supplement and as medicine in most African countries where malaria is also endemic. Therefore, co-administration of MO with antimalarials is a possibility. This study investigated the effects of MO leaves powder on the pharmacokinetics of amodiaquine (AQ) in human subjects., Methods: Twenty healthy volunteers were recruited for the 3-period study. In the first period, a single dose of AQ tablet (10 mg/kg) was administered orally after an overnight fast. After a 7-day washout period, AQ was co-administered with MO. For the third period, each subject took 3 g MO once daily for 7 days and on the 8th day, MO was co-administered with AQ. The plasma concentrations of amodiaquine and desethylamodiaquine (DEAQ) were simultaneously determined using a validated HPLC method., Results and Discussion: The results showed a significant decrease (P = .037) in the Cmax of AQ after concurrent administration (CA) with MO, whereas after pretreatment (PT), there was a 32% decrease in the C max of AQ. For the metabolite, DEAQ, C max increased significantly (P = .006) by 79.36%, and Cmax in PT was significantly higher than (P = .001) that of the CA arm of the study. AUC of DEAQ increased significantly by 40.4% (P = .006) and by 188% (P = .001) after CA and PT, respectively., What Is New and Conclusion: The study established pharmacokinetic interaction between AQ and MO when given together or following a long period of ingestion of MO. This may have clinical implications for malaria therapy., (© 2018 John Wiley & Sons Ltd.)

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.

Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats., (Copyright © 2017. Published by Elsevier Inc.)

Recently, there has been increasing interest in Hypericum (Hypericaceae) genus. The first part of the present study focused on the phytochemical analysis of the methanolic and aqueous extracts of Hypericum humifusum leaves. The second part of the study investigated the effect of Hypericum humifusum leaf extracts on male reproductive parameters. 30 male rats were grouped into control (1mL/rat, distilled water), treated by 200mg/kg body weight (bw) aqueous extract (A200), 400mg/kg bw aqueous extract (A400), 10mg/kg bw methanolic extract (M10) and 20mg/kg bw methanolic extract (M20) groups. The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. After thirty-day treatment, body and reproductive organs were weighed. Testes in all rat groups were processed for biochemical assays and histopathological examinations. Epididymis sperm analyses were also performed. Testicular tissue homogenate samples were used for Malondialdehyde (MDA), catalase and superoxide dismutase (SOD) measurements. We showed that Hh extracts induced a severe seminiferous tubular damage with an increase in the percentage of empty seminiferous tubules. Epididymis sperm analysis revealed a significant reduction in density and viability of sperm with alteration of spermatozoa morphology. Also, we found that Hh leaf extracts decreased plasma total cholesterol, HDL-cholesterol and triglycerides levels. These results were associated with an increase of MDA levels and a decrease of catalase and SOD activities in testis tissues. Our finding revealed that chronic consumption of Hh extracts induces disruption of normal spermatogenesis by alteration of sperm density, viability, and morphology. This action may be due to an inhibition of the antioxidant-defense system., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background and Objective: Lipid transfer protein (LTP) sensitization is the most common cause of food allergy in the Mediterranean area, with peach allergy acting as the primary sensitizer in most cases. Lettuce has been described as a common offending food in patients with LTP syndrome. The aim of the study was to investigate the frequency and clinical expression of LTP syndrome in a sample of lettuceallergic patients., Methods: We determined specific IgE to Pru p 3 and lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms elicited by other LTP-containing plant-derived foods and the presence of cofactors were assessed., Results: The clinical symptoms of lettuce allergy were frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the patients had allergic reactions to other plant foods. Cofactors were involved in the clinical reactions of 13 of the 30 patients. Sensitization to pollens was found in 90% of patients., Conclusions: Lettuce allergy is found not as an isolated condition but in the context of LTP syndrome and it is characterized by severe reactions and frequent cofactor association.

Organic foods have risen in popularity recently. However, the increased risk of bacterial contamination of organic foods has not been fully evaluated. In this study, 100 samples each of organic and conventional fresh vegetables (55 lettuce samples and 45 sprout samples) sold in South Korea were analyzed for aerobic bacteria, coliforms, Escherichia coli, and Bacillus cereus. Although the aerobic bacteria and coliform counts were not significantly different between the two farming types (p > 0.05), the occurrence rate of B. cereus was higher in organically cultivated vegetables compared with those grown conventionally (70% vs. 30%, respectively). The mean contamination level of B. cereus-positive organic samples was also significantly higher (1.86 log colony-forming unit [CFU]/g vs. 0.69 log CFU/g, respectively) (p < 0.05). In addition, six samples of organic vegetables were found to be contaminated with B. cereus at over 4 log CFU/g categorized as unsatisfactory according to Health Protection Agency guideline. The relatively higher occurrence rate of B. cereus in organic vegetables emphasizes the importance of implementing control measures in organic vegetable production and postharvest processing to reduce the risk of food poisoning.

Background: Two outbreaks of gastroenteritis occurred in South Korea, affecting a middle school in the Jeollanam-do province in 2013 (Outbreak 1) and 10 schools in the Incheon province in 2014 (Outbreak 2). We investigated the outbreaks to identify the pathogen and mode of transmission., Methods: A retrospective cohort study was conducted in the Outbreak 1; and case-control studies were performed for the Outbreak 2. Samples from students, environments, and preserved food items were collected and pulsed-field gel electrophoresis (PFGE) was conducted to identify strains of pathogen., Results: We identified 167 and 1022 students who met the case definition (≥3 loose stools in any 24-h period) in the Outbreaks 1 and 2, respectively. The consumption of cabbage kimchi and young radish kimchi were significantly associated with the illness. Adjusted odds ratios of kimchi were 2.62-11.74. In the Outbreak 1, cabbage kimchi was made and consumed in the school restaurant and in the Outbreak 2, young radish kimchi was supplied by food company X and distributed to all the 10 schools in the Incheon province. Enterotoxigenic Escherichia coli (ETEC) O6 was isolated from fecal samples in 375 cases (33.9%) and from kimchi samples. PFGE patterns of the outbreak strains isolated from cases and food were indistinguishable in each outbreak., Conclusion: The suspected food vehicle in these two consecutive outbreaks was kimchi contaminated with ETEC O6. We recommend continued monitoring and stricter sanitation requirements for the food supply process in Korea, especially in relation to kimchi.

Background: Foodborne illness is a continuing public health problem in the United States. Although outbreak-associated illnesses represent a fraction of all foodborne illnesses, foodborne outbreak investigations provide critical information on the pathogens, foods, and food-pathogen pairs causing illness. Therefore, identification of a food source in an outbreak investigation is key to impacting food safety., Objective: The objective of this study was to systematically identify outbreak-associated case demographic and outbreak characteristics that are predictive of food sources using Shiga toxin-producing Escherichia coli (STEC) outbreaks reported to Centers for Disease Control and Prevention (CDC) from 1998 to 2014 with a single ingredient identified., Materials and Methods: Differences between STEC food sources by all candidate predictors were assessed univariately. Multinomial logistic regression was used to build a prediction model, which was internally validated using a split-sample approach., Results: There were 206 single-ingredient STEC outbreaks reported to CDC, including 125 (61%) beef outbreaks, 30 (14%) dairy outbreaks, and 51 (25%) vegetable outbreaks. The model differentiated food sources, with an overall sensitivity of 80% in the derivation set and 61% in the validation set., Conclusions: This study demonstrates the feasibility for a tool for public health professionals to rule out food sources during hypothesis generation in foodborne outbreak investigation and to improve efficiency while complementing existing methods.

Heavy metals (As, Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn) in various vegetables (cabbage, green onion, lettuce, parsley, rocket, spinach, carrot, onion, potato and cauliflower) from the market in Jordan were measured using inductively coupled plasma-mass spectrometry. As, Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn ranged from 0.009-0.275 mg kg(-1) wet weight, 0.004-0.060 mg kg(-1), 0.003-0.401 mg kg(-1), 0.105-3.51 mg kg(-1), 0.15-1.15 mg kg(-1), 0.93-14.39 mg kg(-1), 0.044-0.702 mg kg(-1), 0.072-0.289 mg kg(-1) and 2.23-6.65 mg kg(-1), respectively. Parsley, followed by spinach, contained the highest concentration of heavy metals. Onion contained high levels of toxic heavy metals. The content of Cu in parsley and spinach and Pb in onion exceeded the Codex limits. However, the daily intake of heavy metals from the tested vegetables was lower than the maximum limits for allowable intake.

When the genetically modified soybean is planted in the field, the expression product of exogenous gene could be exposed in the soil ecosystem and bring potential risk to the soil fauna, with the form of leaves and other debris. A few of genetically modified soybeans developed by China independently were used in our study as materials. They were Phytophthora-resistant soybean harboring hrpZm gene (B4J8049), leaf-feeding insect-resistant soybean harboring Cry1C gene (A2A8001) and Leguminivora glycinivorella-resistant soybean harboring Cry1Iem gene (C802). By feeding Folsomia candida with the three genetically modified soybeans for continuous 60 days, the surviving rate, reproductive rate and changes on the body length of F. candida were studied. The results showed that all the three genetically modified soybeans of B4J8049, A2A8001 and C802 had no significant adverse effects on the growth of F. candida, as an environmental indicator organism. It was initially inferred that they were environmentally safe under short-term exposure, which provided basic data of ecological safety for their wide cultivation.

Background: Information regarding the safety of herbal drugs is often not reported. We describe the case of a 65-year-old woman referred to us for a iatrogenic hypercortisolism, who denied any previous steroid consumption. She reported only a chronic application of a phytocosmetic cream, containing ethanol extract of the Cardiospermum halicacabum (CH) plant. Adrenal insufficiency occurred after the cream application was stopped. CH is used in traditional and Western medicine for its documented anti-inflammatory properties. Once the presence of synthetic glucocorticoids was ruled out in the phytocosmetic product, we investigated whether and how its chronic application could have caused the iatrogenic hypercortisolism., Methods: Liquid chromatography high-resolution mass spectrometry (LC-HRMS) was performed to exclude the presence of known glucocorticoids in the cream. ELISA assay and Western blot analysis were employed to assess ACTH secretion and the glucocorticoid receptor expression respectively in murine ACTH-secreting pituitary adenoma cells AtT-20/D16v-F2, treated with dexamethasone, CH tincture, and mifepristone alone or in combination. To detect specific interaction of CH extract with the glucocorticoid receptor, we performed a dual-luciferase reporter assay in HEK293 cells., Results: In AtT-20/D16v-F2 cells, CH extract showed to significantly reduce basal and CRH-induced ACTH secretion and the glucocorticoid receptor expression, similarly to dexamethasone; these effects were counteracted by mifepristone. In HEK293 cells, dexamethasone significantly induced luciferase activity after 24- and 36-hour treatment and CH tincture only after 36 hours; these effects were antagonized by mifepristone., Conclusions: CH extract displays a glucocorticoid-like activity, by means of a direct binding to the glucocorticoid receptor.

The safety of steviol glycosides is based on data available on several individual steviol glycosides and on the terminal absorbed metabolite, steviol. Many more steviol glycosides have been identified, but are not yet included in regulatory assessments. Demonstration that these glycosides share the same metabolic fate would indicate applicability of the same regulatory paradigm. In vitro incubation assays with pooled human fecal homogenates, using rebaudiosides A, B, C, D, E, F and M, as well as steviolbioside and dulcoside A, at two concentrations over 24-48 h, were conducted to assess the metabolic fate of various steviol glycoside classes and to demonstrate that likely all steviol glycosides are metabolized to steviol. The data show that glycosidic side chains containing glucose, rhamnose, xylose, fructose and deoxy-glucose, including combinations of α(1-2), β-1, β(1-2), β(1-3), and β(1-6) linkages, were degraded to steviol mostly within 24 h. Given a common metabolite structure and a shared metabolic fate, safety data available for individual steviol glycosides can be used to support safety of purified steviol glycosides in general. Therefore, steviol glycosides specifications adopted by the regulatory authorities should include all steviol glycosides belonging to the five groups of steviol glycosides and a group acceptable daily intake established., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35-year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips.

The haematological and biochemical parameters of 24 growing Red Sokoto bucks (9.00 ± 0.25 kg body weight) fed threshed sorghum top (TST) with or without five different browse plant foliage Afzelia africana (AA), Daniellia oliveri (DO), Piliostigma thonningii (PT), Pterocarpus erinaceus (PE) and Annona senegalensis (AS) supplements were studied using a completely randomized design. All haematological parameters were (P < 0.05) lower in TST-fed goats compared with TST-supplemented goats, except for mean corpuscular haemoglobin concentration (MCHC), lymphocytes and monocytes which did not follow a particular pattern. Packed cell volume, haemoglobin and monocytes were higher for AA-supplemented goats while MCHC was reduced relative to other supplements (P < 0.05). White blood cell counts were increased in DO lambs compared to other supplements (P < 0.05). Serum proteins, creatinine, alanine transaminase and alkaline phosphate were reduced in TST compared with the supplements (P < 0.05). Cholesterol was higher for PT and AA than other diets (P < 0.05). Aspartate transaminase was reduced in TST goats relative to the supplements (P < 0.05). Except for potassium which was reduced in AS (P < 0.05), all serum major minerals were similar among diets. Results indicate that the entire browse fodder are good supplements to low-quality TST, though A. africana appears to have a better supplementary effect on haematological and biochemical parameters of the goats.

Objective: To determine the effects of decoction derived from the leaves of Nicotiana tabacum (L.) as a mouthwash on minor recurrent aphthous., Methods: A randomized double-blinded placebo-controlled clinical trial was conducted on 60 patients with minor recurrent aphthous. Treatment comprised of application of tobacco or placebo mouthwash (10 mL 3 times a day) for 5 days. Clinical evaluation included pain level using a visual analog scale and ulcer size on days 1, 3, and 5 were measured. Adverse effects after mouthwash application were recorded, and the oral mucosa was examined by the investigator at each visit., Results: A total of 54 subjects with the mean age (38 ± 10) years fulfilled the study. No minor and major adverse effects were observed. In the treatment group, ulcer pain score was decreased by 79.2% and 93.8% and ulcer size was reduced by 69.1% and 92.2% (days 3 and 5, respectively), which was significantly greater than the control group (P < 0.01)., Conclusion: The decoction prepared with of Nicotiana tabacum leaves, used as mouthwash are well-tolerated and safe, and can be used for the management of recurrent aphthous.

There have been very limited reports of the euphoria experienced under the influence of Coleus blumei--part of a large genus with similarities to various mints and herbs, naturally found in abundance and popular in home gardens. There have been reports of similar properties to Salvia divinorum, which contains the psychoactive neocleordane diterpene salvinorin-A. We present a case of a man in his twenties, with no significant known personal or family psychiatric history, presenting to an emergency room with a psychotic episode after the ingestion of C. blumei. He had chewed leaves of this plant, with the intention of obtaining a euphoric experience, as learned through social media posts. Comprehensive laboratory work-up drug screening and diagnostic imaging were negative. Vital signs were stable and physical examination was unremarkable. His mental status improved significantly after treatment with risperidone 2 mg twice daily, during a 5-day psychiatric hospitalization. This case draws attention to a potential psychotropic that warrants clinical consideration and further investigation.

Air pollution causes serious problems in spring in northern China; therefore, studying the ability of different plants to accumulate particulate matter (PM) at the beginning of the growing season may benefit urban planners in their attempts to control air pollution. This study evaluated deposits of PM on the leaves and in the wax layer of 35 species (11 shrubs, 24 trees) in Beijing, China. Differences in the accumulation of PM were observed between species. Cephalotaxus sinensis, Euonymus japonicus, Broussonetia papyriferar, Koelreuteria paniculata and Quercus variabilis were all efficient in capturing small particles. The plants exhibiting high amounts of total PM accumulation (on leaf surfaces and/or in the wax layer), also showed comparatively high levels of PM accumulation across all particle sizes. A comparison of shrubs and trees did not reveal obvious differences in their ability to accumulate particles based on growth form; a combination of plantings with different growth forms can efficiently reduce airborne PM concentrations near the ground. To test the relationships between leaf traits and PM accumulation, leaf samples of selected species were observed using a scanning electron microscope. Growth forms with greater amounts of pubescence and increased roughness supported PM accumulation; the adaxial leaf surfaces collected more particles than the abaxial surfaces. The results of this study may inform the selection of species for urban green areas where the goal is to capture air pollutants and mitigate the adverse effects of air pollution on human health.

Background: Qat (also known as Khat, Kat and Miraa) is a green-leaved plant (Catha edulis). It is a shrub indigenous to Yemen and certain parts of eastern Africa. Chewing the leaves, which have sympathomimetic and euphoric effects, has been documented in many countries and increased with worldwide migration. The effect of long-term chewing Qat on the oral cavity is unknown., Objective: A systematic review was performed to identify any associations between Qat chewing and the occurrence of potentially malignant and malignant oral disorders., Methods: Medline and the Web of Science were searched for articles published before May 2014 without limits with regard to publication date and language., Results: From a total of 890 papers identified, 17 English papers reported potentially malignant or malignant oral disorders and Qat chewing. One additional paper in Arabic language was identified from reviewing the list of references of eligible papers. It was found that exposure to Qat may be associated with potentially malignant and malignant oral disorders, but methodological issues, such as inadequate study design, sample size, selection of study subjects, clinical evaluations of outcome and limited adjustment for confounders, limit the strength of the evidence base in this area., Conclusion: The association between Qat chewing and potentially malignant and malignant oral disorders remains debatable and requires further investigations.

The chewing of khat leaves is an established tradition in East Africa but is much less prevalent in other areas of the world and is mostly limited to Somali communities. However, our understanding of what constitutes problematic khat use in the Somali community in Victoria, Australia, is limited. The objectives of this study were to better understand the views of Somali community representatives and primary care practitioners regarding problematic khat use, to consider relevant harm minimisation strategies, and to develop resources to assist individuals with problematic khat use and their families. Qualitative research methods were used to investigate the experiences and perceptions of khat use among Somalis and mainstream primary care practitioners. Six focus groups were conducted with 37 members of the Somali community and 11 primary care practitioners. Thematic analysis was used to analyse transcripts. Various indicators of the problematic use of khat were identified, including adverse physical and mental health effects, social isolation, family breakdown, and neglect of social responsibilities. Potential harm minimisation strategies were identified including the adoption of health promotion through education, outreach to the community, and the use of universal harm minimisation strategies specifically tailored to khat use.

Khat, an "amphetamine-like green leaf," may influence the consumption of tobacco. This study reviews the epidemiology of tobacco use among khat users. Electronic database searches using appropriate keywords/terms were conducted to identify observational studies of khat use. Assessment of quality and risk of bias of all included studies was conducted, and the results were synthesised descriptively. Nine eligible cross-sectional studies were identified. All assessed self-reported tobacco among khat users and were carried out in Africa and the Middle East. Eight reported cigarettes and one reported waterpipes as the mode of use. Methods of tobacco use prevalence assessment varied. Prevalence of "current" tobacco use among students and university teachers ranged from 29 to 37%; "lifetime" tobacco use in university teachers was 58% and "undefined" tobacco use in nonspecific adults and students ranged from 17 to 78%. Daily tobacco use among adults was reported as 17% whilst simultaneous tobacco and khat use was reported as between 14 and 30% in students. In conclusion, tobacco prevalence among khat users appears significant. Findings should be interpreted cautiously due to self-reported tobacco use, diversity in questions assessing tobacco use, and type of tobacco consumption. Future research should address the methodological shortcomings identified in this review before appropriate policy interventions can be developed.

Guava (Psidium guajava L.) leaf extracts have antiviral and antibacterial activity against shrimp pathogens such as yellow-head virus (YHV), white spot syndrome virus (WSSV), and Vibrio harveyi, which make it a potential water disinfectant for use in shrimp culture. In this study, the safety of guava leaf supplementation in shrimp was evaluated by studying its influence on growth and the non-specific immune response of Penaeus monodon. Six diets containing different levels of guava leaves (0% [basal diet], 0.025% [G1], 0.05% [G2], 0.1% [G3], 0.2% [G4], and 0.4% [G5]) were fed to groups of shrimp (1.576 ± 0.011 g body weight) in triplicate for 56 days. Growth performance (final body weight, WG, PWG, SGR) of shrimp fed guava leaf diets was significantly higher (P < 0.05) than that of shrimp fed on the basal diet. The G1 diet resulted in the highest body weight gain (308.44%), followed by the G2 (295.45%), G3 (283.05%), G5 (281.29%), G4 (276.11%), and finally the basal diet (214.58%). Survival of shrimp in the G1 diet group was higher than that of shrimp in the control and the other experimental groups; however, no statistical differences (P > 0.05) were found. Dietary supplementation with guava leaf improved the activities of prophenoloxidase (PO) and nitric oxide synthase (NOS) in serum, and of superoxide dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LSZ) both in serum and hepatopancreas of shrimp. In the experimental groups, the activities of these enzymes followed a similar pattern of change; they increased initially at low levels of dietary supplementation and then decreased with increasing concentrations of dietary guava leaf. Serum PO and SOD activities in shrimp fed the G1 diet reached 7.50 U ml(-1) and 178.33 U ml(-1), respectively, with PO activity being significantly higher than in controls. In shrimp fed the G1 diet, SOD, ACP, and AKP activities in hepatopancreas were significantly higher than in the controls, reaching 57.32 U g(-1), 23.28 U g(-1), and 19.35 U g(-1) protein, respectively. The highest activities of serum ACP, AKP, LSZ, and of hepatopancreas LSZ, were observed in the G3 diet group. Total nitric oxide synthase (TNOS) activity was highest (64.80 U ml(-1)) in the G4 diet group, which was significantly higher than that observed in the control group. These results suggest that dietary guava leaf supplementation could enhance the growth performance and non-specific immune response of P. monodon. Therefore, guava leaf is considered safe for use as a water disinfectant in shrimp culture., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Safety profiles of the aloe chromone aloesin or Aloe vera inner leaf fillet (Qmatrix) as a well tolerated entity have been reported separately. UP780, a standardized composition of aloe chromone formulated with an Aloe vera inner leaf fillet, has shown a significant beneficial effect in lowering blood glucose and improving insulin resistance in human. Here we evaluate the safety of UP780 after a repeated 14 and 90-day oral administration in CD-1 mice. UP780 was given at doses of 100mg/kg/day, 500mg/kg/day and 1000mg/kg/day to groups of 10 male and 10 female for 90days or administered by oral gavage at a dose of 2g/kg/day to groups of 5 male and 5 female for 14days. Body weight, feed consumption, hematology, clinical chemistry and histopathologic evaluation were performed. UP780 at a dose of 1000mg/kg/day or at 2000mg/kg/day produced no treatment-related toxicity or mortality. Body weight gain or feed consumption was similar between groups. There was no test article-related microscopic change. Spontaneously occurring minor changes in clinical chemistry and hematology were observed. However, these changes were limited to one sex or were not dose correlated. UP780 was well tolerated in this strain. A dose of 2000mg/kg/day was identified as the NOAEL (no-observed-adverse-effect-level)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Khat (Catha edulis) is widely used in East Africa and the Middle East, often in combination with tobacco smoking. Sleep disturbance has been linked with habitual khat use; however, no systematic attempt has been made to test the hypothesis that use of khat and khat and tobacco in combination are related to sleep disturbance. Sleep disturbances are associated with dysregulations in emotional and physiological functions and can increase health risks., Methods: We developed and used the Arabic version of the Pittsburgh Sleep Quality Index (PSQI) to conduct a cross-sectional study in Yemen examining subjective sleep quality in 151 concurrent users of khat and tobacco, 141 khat-only users, and 92 nonusers. Measures on subjective mood were also collected. A series of analyses of variance and χ(2) tests were conducted to test whether khat and tobacco use was linked with sleep disturbances., Results: Concurrent users of tobacco and khat and khat-only users showed greater sleep disturbances than nonusers as assessed by the PSQI global scores (all P values < .001) and component scores. PSQI scores were correlated with negative and positive mood (all P values < .004)., Conclusion: Sleep disturbances may be 1 mechanism of the link between khat, tobacco, and negative health outcomes. Our findings may be useful in developing targeted prevention and harm-reduction strategies to minimize health care burdens associated with these substances. Our study also provides initial support for the Arabic version of PSQI.

Background: Sainfoin (Onobrychis viciifolia Scop.) is a forage legume found in temperate areas but is less widespread in Mediterranean environments. Compared with other perennial legumes, it has the advantage of containing condensed tannins (CT) that can be important for their implications on ruminant nutrition and health. Data on nitrogen (N) fixation by sainfoin in the literature originate from very different environments and only a few field data are available, so it is important to improve knowledge on the N fixation potential of this species, particularly under a Mediterranean climate. Here the accumulation pattern of polyphenolic compounds (total, non-tannic polyphenols and CT) and the N fixation potential of sainfoin were studied in order to contribute to its valorisation for sustainable farming management in Mediterranean environments., Results: CT concentrations were always in the range considered beneficial for animals, not exceeding 50 g delphinidin equivalent kg⁻¹ dry matter (DM). The regression of aerial fixed N on aerial DM showed a relationship of 22 kg fixed N t⁻¹ aerial DM in a Mediterranean environment., Conclusion: A wider exploitation of sainfoin is suggested for production under rain-fed conditions, thus enlarging the limited set of available perennial legumes suitable for Mediterranean environments., (© 2013 Society of Chemical Industry.)

In the European Union almost 300,000 tons of raw tobacco are produced every year, contributing for 4% of the world production. In Italy, tobacco crop produces around 90,000 tons/year and is concentrated in Veneto, Tuscany, Umbria and Campania Regions. In 1970, Common Market Organisation provided a virtually unlimited support for European tobacco production. After 2004, funds progressively has been cut by half, even though the other half has been given for restructuring or reconversion of tobacco farms through the Rural Development Plan. The Framework Convention on Tobacco Control recommends conversion of tobacco crops, although there are no effective measures. Tobacco production requires large quantities of chemicals (pesticides, growth regulators, fertilisers), with significant workers' exposure if applied without personal protective equipments. Pesticides may have genotoxic, teratogenic, immunotoxic, hormonal, and carcinogenic effects. Tobacco itself may cause also a disease called "Green tobacco sickness" syndrome, as a consequence of nicotine dermal absorption due to skin exposure to tobacco leaves. In Italy, financial resources for tobacco production and restructuring/conversion to other crops of previously tobacco planted fields are available. On the contrary, anti-smoking media interventions do not receive funds comparatively relevant as those for tobacco production.

Background: Tobacco in any form (smoking or chewing), arecanut chewing, and alcohol are considered to be the major extrinsic etiological factors for potentially malignant disorders of the oral cavity and for squamous cell carcinoma, the most common oral malignancy in India. An increase in nuclear diameter (ND) and nucleus-cell ratio (NCR) with a reduction in cell diameter (CD) are early cytological indicators of dysplastic change. The authors sought to identify cytomorphometric changes in ND, CD, and NCR of oral buccal cells in tobacco and arecanut chewers who chewed with or without betel leaf., Methods: Participants represented 3 groups. Group I consisted of 30 individuals who chewed tobacco and arecanut with betel leaf (BQT chewers). Group II consisted of 30 individuals who chewed tobacco and arecanut without betel leaf (Gutka chewers). Group III comprised 30 apparently healthy nonabusers. Cytological smears were prepared and stained with modified-Papanicolaou stain., Results: Comparisons between Groups I and II and Groups II and III showed that ND was increased, with P values of .054 and .008, respectively, whereas a comparison of Groups I and III showed no statistical significance. Comparisons between Groups I and II and Groups II and III showed that CD was statistically reduced, with P values of .037 and <.000, respectively, whereas comparison of Groups I and III showed no statistical significance. Comparisons between Groups I and II and groups II and III showed that NCR was statistically increased, with P values of <.000, whereas a comparison of Groups I and III showed no statistical significance., Conclusions: CD, ND, and NCR showed statistically significant changes in Group II in comparison with Group I, which could indicate larger and earlier risk of carcinoma for Gutka chewers than in BQT chewers.

Aims: The present study assessed whether cigarette smokers who are also regular khat users would demonstrate greater impairments in verbal learning and recall compared to both non-smokers who are khat users and control subjects., Design: An independent-measures, between-subjects design with two covariates., Setting: An out-patient, university research center in Taiz, Yemen., Participants: Subjects were 175 Yemeni college students (90 men, 85 women) ranging in age from 18 to 38 years. Seventy-five subjects were self-reported chronic cigarette smokers and khat users, 48 non-smoking subjects were self-reported to be chronic khat users and 52 non-smoking subjects reported no current use or history of khat use., Measurements: Verbal learning and verbal memory recall was assessed by subject performance on the Arabic version of the Rey Auditory Verbal Learning Test (RAVLT)., Findings: Statistically significant differences (P < 0.05) were observed in RAVLT acquisition learning trials 2-5 and on delayed recall measures between concurrent khat and cigarette users compared to both the khat-only group and the control group of non-users of khat and cigarettes. On each of these trials, concurrent users recalled fewer words, demonstrating a slowed rate of verbal learning. This same pattern of performance was also seen on delayed recall measures. Khat use alone did not affect immediate or delayed recall of previously learned words., Conclusions: Khat users who smoke cigarettes have a lower rate of verbal learning and delayed recall of previously learned verbal material than khat users who do not smoke cigarettes. This may be due to pre-existing differences between these groups of subjects., (© 2013 Society for the Study of Addiction.)

Regular consumption of khat's (Catha edulis) fresh leaves seriously affects the health, the social and economic life of the subject. Therefore, it is hazardous both to the individual and to the community. According to the latest reports, consumption of chat may exert some unknown and unreported gastrointestinal and hepatic effects. On the basis of studies performed by the authors, it seems that khat (cathinone) has no gastric or duodenal ulcerogenic effect. However, it does cause a significant enlargement of the hepatic mitochondria. In addition, a concern arose recently that the profit of illegal traffic of the plant may reach some illegal (terrorist) organisations. Therefore it seems that the so-called "khat-problem" needs further and more effective control.

An evidence-based systematic review of kratom (Mitragyna speciosa) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Background: Stevia rebaudiana Bertoni has been used for the treatment of diabetes in, for example, Brazil, although a positive effect on antidiabetic and its complications has not been unequivocally demonstrated. This herb also has numerous therapeutic properties which have been proven safe and effective over hundreds of years. Streptozotocin is a potential source of oxidative stress that induces genotoxicity., Objective: We studied the effects of stevia leaves and its extracted polyphenols and fiber on streptozotocin induced diabetic rats. We hypothesize that supplementation of polyphenols extract from stevia to the diet causes a reduction in diabetes and its complications., Design/methods: Eighty Wistar rats were randomly divided into 8 groups; a standard control diet was supplemented with either stevia whole leaves powder (4.0%) or polyphenols or fiber extracted from stevia separately and fed for one month. Streptozotocin (60 mg/kg body weight, i.p) was injected to the diabetic groups on the 31st day. Several indices were analyzed to assess the modulation of the streptozotocin induced oxidative stress, toxicity and blood glucose levels by stevia., Results: The results showed a reduction of blood glucose, ALT and AST, and increment of insulin level in the stevia whole leaves powder and extracted polyphenols fed rats compared to control diabetic group. Its feeding also reduced the MDA concentration in liver and improved its antioxidant status through antioxidant enzymes. Glucose tolerance and insulin sensitivity were improved by their feeding. Streptozotocin was also found to induce kidney damage as evidenced by decreased glomerular filtration rate; this change was however alleviated in the stevia leaves and extracted polyphenol fed groups., Conclusion: The results suggested that stevia leaves do have a significant role in alleviating liver and kidney damage in the STZ-diabetic rats besides its hypoglycemic effect. It might be adequate to conclude that stevia leaves could protect rats against streptozotocin induced diabetes, reduce the risk of oxidative stress and ameliorate liver and kidney damage., (Copyright © 2013 Elsevier Inc. All rights reserved.)