Histological and body weight effects of Datura innoxia seeds and leaves extracts in rats

The study aim to determine the chemical compounds in aqueous and methanolic extracts of Datura innoxia seeds and leaves and to evaluate their toxic effects on experimental rats. Seeds and leaves were collected from El-Obied, North Kordofan State, Sudan, in October, 2016. The aqueous and methanol extracts were carried out by using maceration method and soxhlet apparatus respectively. Sixty five male Albino Wistar rats, three months old and with an average body weight ranged 110-120 g, were randomly divided into thirteen Groups, consisting of five rats in each Group. Group 1 served as control and fed with normal rats’ food and water for thirty days. Groups 2, 6 and 10 administered aqueous seeds extract, Groups 4, 8 and 12 received methanol seeds extract, Groups 3, 7 and 11 received aqueous leaves extracts, Groups 5, 9 and 13 received methanol leaves extract, all the Groups received the same type of extract were administered 40, 60 and 80 mg/kg body weight respectively. The extracts administered to the rats intra gastrically using cathodal tube daily for thirty days. The effects of oral administration of leaves and seeds extracts to 60 healthy rats over 30 days were evaluated by histological studies and body weight changes. The analysis by gas chromatography-mass spectrometry (GC-MS) of aqueous and methanolic extracts revealed the presence of alkaloids (Scopolamine, atropine and Hyoscyamine), fatty acids, esters, amides, amino acids, ketones, coummarins, terpinoids, phenols, alcohols and hydrocarbons compounds. The histological results showed that administration of extracts caused pathologic changes in the organs studied. The treated Groups had lower (p ≤ 0.05) body weight gains than control Group. The study concluded that the toxicity of seeds and leaves (methanolic and aqueous) extracts are nearly have the same toxic effects on rats due to their same active ingredients (alkaloids) and the oral administration of the extracts was found to be safe up to 40 mg/kg.

Download Full-text

The Effect of Datura Innoxia Seeds and Leaves Contents on Albino Wister Rats

Journal of Pharmaceutical Research and Development ◽

10.47485/2694-5614.1004 ◽

2020 ◽

Keyword(s):

Body Weight ◽

Oral Administration ◽

Stomach Contents ◽

Chemical Compounds ◽

The Body ◽

Gas Chromatography Mass Spectrometry ◽

Datura Innoxia ◽

Methanolic Extracts ◽

Zn Concentration ◽

New Compounds

The aim of the study was to evaluate the toxic effect of Datura innoxia seeds and leaves on experimental rats by determining the elements content of seeds and leaves, the chemical compounds in aqueous and methanolic extracts of seeds and leaves and the chemical compounds in the stomach content of rats. Seeds and leaves were collected from El-Obied, North Kordofan State, Sudan, in October, 2016. The aqueous and methanol extracts were carried out by using maceration method and soxhelt apparatus respectively. Sixty five male albino wister rats, three months old and with an average body weight ranged 110-120 g, were randomly divided into thirteen groups, consisting of five rats in each group. Group 1 served as control and fed with normal rats food and water for thirty days. Groups 2, 6 and 10 administered aqueous seeds extract, groups 4, 8 and 12 received methanol seeds extract, groups 3, 7 and 11 received aqueous leaves extracts, groups 5, 9 and 13 received methanol leaves extract, all the groups received the same type of extract were administered 40, 60 and 80 mg/kg body weight respectively. The extracts administered to the rats intra gastrically using cathodal tube daily for thirty days. The elements in the leaves and seeds (K, Ca, S, Si, Cl, Fe, Al, P, Mg, Ti, Mn, Zn, Sr, Cu, V, Br and Zr) were determined by energy-dispersive X-ray fluorescence (EDXRF) spectroscopy. K content was the highest in seeds (5.469 ± 0.021%), Ca and S the highest in leaves (2.461 ± 0.019%, 1.254 ± 0.022 % respectively). The elements Ti, Mn, Sr, V, Br and Zr were detected in the leaves with range concentration 0.062-0.002%. The elements Si, Cl, Fe, Al, P, Mg and Zn concentration in seeds varied from 0.002 to 0.942% and in leaves varied from 0.014 to 0.346%. The concentration of these elements did not exceed the standard dangerous toxic levels. The effects of oral administration of leaves and seeds extracts to 60 healthy rats over 30 days were evaluated by monitoring the chemical changes of stomach contents. The analysis by gas chromatography-mass spectrometry (GC-MS) of aqueous and methanolic extracts revealed the presence of alkaloids (scopolamine, atropine and hyoscyamine), fatty acids, esters, amides, amino acids, ketones, coummarins, terpinoids, phenols, alcohols and hydrocarbons compounds. New compounds appeared in the stomach contents in the treated groups and this suggest that some compounds were metabolized and circulated in the body after the oral administration of leaves and seeds extract. The study concluded that the toxicity of seeds and leaves (methanolic and aqueous) extracts are nearly have the same toxic effects on rats due to their same active ingredients (alkaloids) and the oral administration of the extracts was found to be safe up to 40 mg/kg.

Download Full-text

A 90-Day Oral Toxicity of Hydroethanolic Root Extract of Carissa spinarum in Wistar Rats

Journal of Toxicology ◽

10.1155/2021/5570206 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Komlan M. Dossou-Yovo ◽

Aboudoulatif Diallo ◽

Povi Lawson-Evi ◽

Yendubé T. Kantati ◽

Tchin Darré ◽

...

Keyword(s):

Body Weight ◽

Biochemical Parameters ◽

Wistar Rats ◽

Hematological Parameters ◽

Relative Weight ◽

Control Group ◽

Root Extract ◽

Weight Changes ◽

Oral Toxicity ◽

Significant Difference

Background. Herbal medication is a worldwide and ancient practice, mostly in developing countries, where a large part of the population is involved in this practice. Hence, studies must be conducted to evaluate their safety and efficiency to avoid or prevent toxicological risks due to their usage. In Togo, Carissa spinarum is a medicinal plant belonging to Apocynaceae family, used as an aphrodisiac or to heal some ailments including malaria, sickle cell anemia, hypertension, pain, and asthma. Notwithstanding its several ethnomedicinal benefits, just a few toxicological data associated with its chronic use are available. Objective. Therefore, this study aims to assess the toxicity of an ethanolic root extract of Carissa spinarum in Wistar rats. Methods. The 90-day oral toxicity process following OECD TG 408 guidelines is used. Male Wistar rats received Carissa spinarum root hydroethanolic extract at 500 and 1000 mg/kg for 90 days by oral gavage. Body weight changes, hematological and blood biochemical parameters, organ weight changes, malondialdehyde as a lipoperoxidation marker expressed according to tissue proteins, and histopathology of vital organs were assessed. Results. No signs of toxicity or mortality were observed during the 90 days experiment. Hematological parameters have not shown any treatment-related abnormalities. According to biochemical parameters, an increase in the chloride ion level was observed at 1000 mg/kg p < 0.01 . There was no significant difference between the treated groups and the control group concerning the malondialdehyde concentration, body weight, and organ relative weight. No changes in necropsy and histopathology of vital organs associated with extract treatment were observed. Conclusion. The results indicated that an ethanolic root extract of Carissa spinarum does not cause adverse effects, which can lead to Wistar rats’ death after 90-day oral administration at 500 and 1000 mg.

Download Full-text

Abstract 1818: Beneficial Effects of Weight Loss Associated with a High Protein Diet on Cardiovascular Risk Profile, Functional Status and Quality of Life in Obese Heart Failure Patients: A Feasibility Study

Circulation ◽

10.1161/circ.116.suppl_16.ii_387-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Lorraine S Evangelista ◽

David Heber ◽

Zhaoping Li ◽

Michele Hamilton ◽

Gregg C Fonarow

Keyword(s):

Heart Failure ◽

Weight Loss ◽

Body Weight ◽

Functional Status ◽

High Protein ◽

Control Group ◽

Long Term Effects ◽

Weight Changes ◽

Cardiovascular Risks ◽

The Impact

OBJECTIVE: Clinical management of chronic heart failure (HF) related to adequate nutritional intake currently lacks a strong scientific basis. This study was conducted to evaluate the impact of 3 diet interventions on body weight and its potential to reduce cardiovascular risks and improve functional status. METHOD: Fourteen obese HF patients (BMI > 27 kg/m2) were randomized to1 of 3 diets: high protein (HP); low fat (LF) or average diet/control group (CG). Body anthropometrics (weight, BMI, waist circumference), indices of cardiovascular risks including (% body fat, blood pressure, cholesterol, triglycerides), and measures of functional status (6-minute walk, max VO2) were obtained at baseline and after a 12-week nutritional support program. Statistics included two-way RMANOVA. RESULTS: There were no significant differences in age (59±10 years), gender (78% male), NYHA (43% class II; 57% class III), HF etiology (57% non-ischemic), or ejection fraction (0.26±0.07) between the groups. The HP diet resulted in moderate reductions in body weight (Figure ) and improvements in several health parameters (Table ). CONCLUSION: The data show that in a small group of obese HF patients, a 12-week HP diet resulted in moderate weight loss that was associated with reduced cardiovascular risks and better functional status. However, the long-term effects of a HP diet remain uncertain. Figure Comparison of Weight Changes in the HP, LF and CG from Baseline to 12 Weeks Mean changes in outcomes from baseline to 12 weeks, by diet group and time

Download Full-text

Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.4.1048 ◽

1996 ◽

Vol 14 (4) ◽

pp. 1048-1054 ◽

Cited By ~ 203

Author(s):

H Wada ◽

S Hitomi ◽

T Teramatsu

Keyword(s):

Lung Cancer ◽

Body Weight ◽

Adjuvant Chemotherapy ◽

Oral Administration ◽

Small Cell Lung Cancer ◽

Survival Rates ◽

Small Cell ◽

Control Group ◽

Small Cell Lung ◽

Control Groups

PURPOSE We performed a study to determine whether postoperative mild chemotherapy to maintain the patient's quality of life (QOL) and immunoactivity could also prolong survival. SUBJECT AND METHODS From December 1985 to July 1988, 323 patients with completely resected primary non-small-cell lung cancer (stage I to III) were enrolled. The subjects were randomized into three treatment groups, as follows: cisplatin (CDDP) 50 mg/m2 body surface, vindesine (VDS) 2 to 3 mg/kg body weight for three courses, and 1-year oral administration of tegafur (FT) plus uracil (UFT) 400 mg/kg body weight (CVUft group, 115 patients); 1-year oral administration of UFT 400 mg/kg body weight (Uft group, 108 patients); or surgical treatment only (control group, 100 patients). RESULTS The overall 5-year survival rates were 60.6% for the CVUft group and 64.1% for the Uft group versus 49.0% for the control group. The results of statistical testing were P = .053 (log-rank test) and P = .044 (generalized Wilcoxon test) among the three groups, P = .083 (log-rank) and P = .074 (Wilcoxon) between the CVUft and the control groups, and P = .022 (log-rank) and P = .019 (Wilcoxon) between the Uft and the control groups, which indicates higher survival rates in the CVUft and the Uft groups compared with the control group. A multivariate statistical analysis on prognostic factors using Cox's proportional hazards model was performed with the following results: P = .037, hazards ratio = 0.64 with a 95% confidence interval (CI) of 0.42 to 0.97 (control v CVUft group); and P = .009, hazards ratio = 0.55 with a 95% CI of 0.36 to 0.86 (control v Uft group). CONCLUSION Significantly favorable results were obtained in the CVUft and Uft groups compared with surgery alone. These data showed significant prognostic advantages in the postoperative adjuvant chemotherapy groups.

Download Full-text

Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

BioMed Research International ◽

10.1155/2013/182064 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 31

Author(s):

Kwan Yuet Ping ◽

Ibrahim Darah ◽

Yeng Chen ◽

Subramaniam Sreeramanan ◽

Sreenivasan Sasidharan

Keyword(s):

Body Weight ◽

Toxicity Study ◽

Morphological Alteration ◽

Control Group ◽

Sprague Dawley ◽

Oral Toxicity ◽

Methanolic Extracts ◽

Sprague Dawley Rats ◽

Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

Download Full-text

Study of acute toxicity of the drug «Kolidev 8M» with a single intragastric injection in laboratory animals

ScienceRise Biological Science ◽

10.15587/2519-8025.2021.235952 ◽

2021 ◽

pp. 44-48

Author(s):

Roman Sachuk ◽

Yaroslav Stravskyy ◽

Bogdan Gutyj ◽

Tetiana Velesyk ◽

Orest Katsaraba ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Administration ◽

Veterinary Drug ◽

Control Group ◽

Intragastric Administration ◽

Toxic Substances ◽

Class Iii ◽

Absolute Weight ◽

Class Iv

«Kolidev 8M» (powder for oral use) is a veterinary drug used to treat ornamental birds (pheasants, peacocks) in diseases of the digestive tract caused by microorganisms sensitive to colistin. In the study of the drug «Kolidev 8M» for oral administration, along with the confirmation of therapeutic properties, it is necessary to determine the LD50 obtained in the process of studying acute toxicity. The aim of research. The aim of research was to determine the acute toxicity of the veterinary drug «Kolidev 8M» (powder for oral administration) under the conditions of intragastric administration to white mice. Materials and methods of research. To achieve this aim, an experiment was conducted on 114 males of nonlinear white mice kept under optimal conditions in the vivarium of DEVIE LLC (Rivne, Ukraine). In the first series of experiments on the principle of analogues was formed control and three experimental groups of 6 animals each (n=6). The drug in the form of a solution was administered once orally using a esophageal gastric tube in doses of 500,0; 2000,0 and 4000,0 mg/kg body weight by absolute weight of the drug. The animals of the control group were injected with distilled water. After taking into account the results of the first experiment in the next experiment, 6 experimental groups were formed – mice, which were administered the drug «Kolidev 8M» in the form of a solution in doses (by absolute weight of the drug) – 500,0; 1000,0; 1500,0; 2000.0; 2500,0; 3000,0; 3500 and 4000,0 mg/kg body weight, as well as the control group – animals that were injected with distilled water with a volume of 0.5 cm3 according to similar regulations (Zapadniuk, 1983; Kotsiumbas, 2005; Karkyshchenko & Hrachev, 2010). There were 6 animals in each group (n=6). After their death, a pathological autopsy was performed (Zharov A. et al., 2003). The average lethal dose of LD50 was calculated by the method of probit analysis by Prozorovsky V.B. Research results. According to the results of research, it was found that the LD50 of the drug «Kolidev 8M» (powder for oral administration) under the conditions of its single intragastric administration to male mice is 2024,72±232,45 mg/kg, LD10 – 392,87 mg/kg, LD16 – 751,56 mg/kg, LD84 – 3297,88 mg/kg, LD90 – 3656,57 mg/kg, LD100 – 3934,47 mg/kg body weight, respectively. According to the results of an acute toxicological experiment with intragastric administration of the drug «Kolidev 8M» to white male mice, LD50 was 2024,72±232,45 mg/kg body weight. This allows, according to toxicity, to refer this drug to class IV – low-toxic substances (LD50 501,0-5000,0 mg/kg body weight), and the degree of danger to class III – moderately safe substances (LD50 151,0-5000,0 mg/kg body weight). Conclusions and prospects for further research. The drug «Kolidev 8M» in terms of toxicity belongs to class IV – low-toxic substances, and the degree of danger to class III – moderately safe substances. Further studies will be the next stage of pre-registration trials aimed at studying the subacute toxicity of the drug «Kolidev 8M»

Download Full-text

Evaluation of acute oral toxicity of herbal rumenotoric and stomachic

The Journal of Phytopharmacology ◽

10.31254/phyto.2021.10501 ◽

2021 ◽

Vol 10 (5) ◽

pp. 282-285

Author(s):

Sunil Hajare ◽

◽

Ranjit Suresh Ingole ◽

Maheshkumar Vitthal Ingawale ◽

Vivek Borekar ◽

...

Keyword(s):

Body Weight ◽

Oral Administration ◽

Adult Female ◽

Blood Biochemistry ◽

Toxic Effects ◽

Test Substance ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Swiss Albino Mice ◽

Common Problems

Maintaining optimum digestive functions is crucial for achieving health and profitability in livestock enterprises. However, the efficiency of these functions is upset by common problems such as indigestion, anorexia, flatulence, ruminal stasis and impaction. Pachoplus™ (M/s Ayurvet Limited, India) is a polyherbal rumenotoric, carminative and stomachic that helps to achieve and restore optimum digestive functions in livestock. A study was undertaken to evaluate the potential of Pachoplus™ to elicit acute oral toxicity as per OECD 423 guidelines. Nine non-pregnant, nulliparous, adult female Swiss albino mice were used for the study. The animals were observed for the manifestation of toxic effects and mortality after the oral administration of the test substance. Toxicity was evaluated on the basis of changes in body weight, overt signs of toxicity, gross and histological appearances of vital organs, and blood biochemistry. Pachoplus™ was found safe for oral use as no toxic effects or mortalities were observed till day 14

Download Full-text

Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits

Human & Experimental Toxicology ◽

10.1177/0960327116637111 ◽

2016 ◽

Vol 36 (1) ◽

pp. 42-50 ◽

Cited By ~ 4

Author(s):

Adil Mehraj Khan ◽

Satyavan Rampal ◽

Naresh Kumar Sood

Keyword(s):

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Body Weight ◽

Oral Administration ◽

Reduced Glutathione ◽

Treated Group ◽

Control Group ◽

Oxidative Balance ◽

Antioxidant Parameters ◽

Elevated Lipid

The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction ( p < 0.05) of reduced glutathione levels was observed in groups treated with meloxicam both alone and in combination with levofloxacin, whereas an increase ( p < 0.01) in the levels of this antioxidant was observed in the groups treated with enrofloxacin. The activities of enzymes, glutathione peroxidase and superoxide dismutase, were induced ( p < 0.05) in levofloxacin-alone treated group. Superoxide dismutase was also induced ( p < 0.05) in meloxicam-alone treated group and inhibited ( p < 0.05) in enrofloxacin-meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher ( p < 0.01) lipid peroxidation than control and levofloxacin-alone treated groups. Elevated lipid peroxidation was also observed in the groups treated with meloxicam both alone and in combination with levofloxacin ( p < 0.05). In conclusion, these drugs have potential to induce oxidative imbalance, however, compared to levofloxacin, more oxidative damage is produced by enrofloxacin and meloxicam.

Download Full-text

Oral Administration of Red Rice (Oryza nivara) Bran Extract Reduced Weight, Visceral Fat And Liver Steatosis Amount in Obesity Male Wistar Rats (Rattus norvegicus)

Neurologico Spinale Medico Chirurgico ◽

10.36444/nsmc.v4i2.154 ◽

2021 ◽

Vol 4 (2) ◽

Author(s):

Dianika Putri Puspitasari ◽

Alex Pangkahila ◽

Ni Nyoman Ayu Dewi

Keyword(s):

Body Weight ◽

Treatment Group ◽

Oral Administration ◽

Rice Bran ◽

Visceral Fat ◽

Wistar Rats ◽

Liver Steatosis ◽

Control Group ◽

Red Rice ◽

Oryza Nivara

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity. Red rice (Oryza nivara) bran is known to contain polyphenol and antioxidants that might be potential in reducing body weight and visceral fat in obese mice and preventing liver steatosis. This study was aimed to prove the effect of oral administration of red rice bran (Oryza nivara) extract on body weight, visceral fat, and liver steatosis amount in obese male Wistar rats. Method: In this research, the subjects were 36 male obese (Lee index > 0.3) white rats (Rattus norvegicus) Wistar strain, 4-5 months old, divided into two groups. The control group received a placebo and the treatment group received 460mg/200gram red rice bran extract for 5-weeks. Bodyweight, visceral fat, and the amount of liver steatosis were observed. Differences between groups in each variable were analyzed. Results: The weight of the control group and the treatment group was 321.17 ± 19.04 grams and 305.72 ± 12.89 grams (p < 0.05). The visceral fat weight was 3.15 ± 0.34 grams in the control group and 2.99 ± 0.34 grams (p > 0.05) in the treatment group. Liver steatosis amount was 41 ± 18 cells per visual field in the control group, and 21 ± 12 (p < 0.05) in the treatment group. Conclusion: Oral administration of red rice bran extract can reduce body weight and liver steatosis amount in obese Wistar rats. The extract of red rice bran did not have a significant effect in reducing visceral fat.

Download Full-text

Effects of Spirulina platensis on alloxan induced diabetic rats

Progressive Agriculture ◽

10.3329/pa.v29i2.38300 ◽

2018 ◽

Vol 29 (2) ◽

pp. 139-146

Author(s):

SMAK Hussaini ◽

MI Hossain ◽

MS Islam ◽

K Rafiq

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Oral Administration ◽

Lipid Profile ◽

Spirulina Platensis ◽

Profile Analysis ◽

Diabetic Control ◽

Diabetic Rats ◽

Male Rats ◽

Control Group

The study was undertaken to investigate the effects of Spirulina platensis on body weight, blood glucose and lipid profile on alloxan induced diabetic rats. Fifteen Long Evans male rats at six weeks of age were used for the experiment. Diabetes was induced by intraperitoneal injection of alloxan@ 150 mg/kg and experiment was carried out for a period of 6 weeks. Rats were divided into three groups of 5 rats each. The groups were i)healthy control, ii) diabetic control with both receiving rats’ pellet as supplement, and iii) diabetic treated with oral administration of Spirulina platensis @ 400 mg/kg bwt. Results from the study showed that Spirulina platensis reduced blood glucose significantly (P<0.01) and increased body weight significantly (P<0.05) in contrast to diabetic control group after 6 weeks. Lipid profile analysis with Spirulina platensis @ 400 mg/kg showed that total cholesterol, plasma triglycerides, and LDL were lowered significantly compared to diabetic groups in contrast to HDL levels which were increased following the use of Spirulina platensis. Our findings showed that oral administration of Spirulina platensis could reduce the adverse effect of alloxan induced diabetes in rats. Based on this research it can be concluded that Spirulina platensis has antihyperglycemic and hypolipidimic effects in alloxan induced diabetic rats.Progressive Agriculture 29 (2): 139-146, 2018

Download Full-text