Comparative Evaluation of the Acute Toxic Effects in Monkeys, Pigs and Mice of a Genetically Engineered Salmonella Strain (VNP20009) Being Developed as an Antitumor Agent

2000 ◽  
Vol 19 (1) ◽  
pp. 19-25 ◽  
Author(s):  
King C. Lee ◽  
Li-Mou Zheng ◽  
Xiang Luo ◽  
Caroline Clairmont ◽  
Jessica Fischer ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Comparative Evaluation ◽  
Clinical Signs ◽  
Clinical Pathology ◽  
Genetically Engineered ◽  
The Body ◽  
Toxic Effects ◽  
Weight Increase ◽  
High Dose ◽  
Physical Damage

The objective of these studies was to perform a comparative evaluation of the acute toxicity of VNP20009, a genetically engineered Salmonella strain, in monkeys, pigs, and mice. It is hypothesized that mice would be more susceptible than other animal species to the toxic effects of VNP20009, because mice are the most sensitive natural host for the parental wild-type Salmonella typhimurium strain. These studies also compared the virulence of VNP20009 and the parental Salmonella in mice. In Cynomolgus monkeys and Yorkshire pigs ( n = 2/dose), various doses (expressed as colony forming units [cfu] per animal) of VNP20009, or vehicle, were administered as a single IV injection (∼ 1 ml/min). The body weight, body temperature, clinical signs, clinical pathology (serum chemistry and hematology), and ophthalmic examinations (only in monkeys) were evaluated at various times. Necropsy was performed on day 15 in the pigs, and necropsy and histopathology on days 8 or 15 in the monkeys. In C57BL/6 mice ( n = 10/dose), various doses of VNP20009, or the parental Salmonella, were administered as a single IV bolus injection. The mice were observed daily over 3 weeks. The results from monkeys showed that VNP20009-related changes in clinical pathology were primarily confined to fiver enzymes and fiver function tests (i.e., cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase levels). Significant toxicological changes occurred only at the dose of 1 × 1010 cfu/monkey, but not at the doses of 1 × 108 or 3 × 109 cfu/monkey. Gross necropsy and histology findings were primarily confined to the spleen (enlargement, weight increase, and reticuloendothelial hyperplasia), thymus (size and weight reduction and lymphoid depletion), mesenteric lymph node (enlargement), and lung (weight increase). Most of these necropsy and microscopic findings, which occurred mostly in the high-dose group, may be related to the physiological responses to infection, rather than related to the intrinsic toxicity of VNP20009. The results from pigs showed that VNP20009 induced toxicological effects only at the dose of 3 × 109 cfu/pig, but not at the doses of 3 × 108 or 3 × 1010 cfu/pig. Both pigs treated with 3 × 1010 cfu/pig died within the first 2 days post-treatment. Necropsy showed the presence of abdominal transudate fluid, skin blotching, and pulmonary-and gall bladder-associated edema. Therefore, the pig mortality may have been related to the physical damage induced by the sudden systemic presence of large amounts of suspension. The results from mice showed that VNP20009, at doses as high as 1 × 106 cfu/mouse, did not induce any mortality. A 30% mortality rate was induced by 3 × 106 cfu/mouse, and 100% mortality by 1 × 107 cfu/mouse. The parental Salmonella, at a dose of 1 × 102 or 3 × 102 cfu/mouse, induced a 100% mortality. In conclusion, the doses of VNP20009 that induced acute toxicity are very high, suggesting that VNP20009 may be a safe agent. The virulence is 50,000 × less in VNP20009 than the parental Salmonella.

scholarly journals A case report of a severe neonatal systemic vasculitis on the first day of life

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Stephanie Wong ◽  
Erkan Demirkaya ◽  
Roberta Berard
Keyword(s):  
Lupus Erythematosus ◽  
Reactive Arthritis ◽  
Index Finger ◽  
Systemic Vasculitis ◽  
Clinical Signs ◽  
The Body ◽  
Oral Steroid ◽  
Left Index Finger ◽  
High Dose ◽  
New Onset

Abstract Background Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren’s syndrome, Behҫet’s disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate. Case presentation In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred. He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy. The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development. Conclusion This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.

scholarly journals ACUTE AND SUB CHRONIC TOXICITY STUDIES OF PURIFIED WITHANIA SOMNIFERA EXTRACT IN RATS

2018 ◽  
Vol 10 (12) ◽  
pp. 41 ◽  
Author(s):  
Benny Antony ◽  
Merina Benny ◽  
Binu T. Kuruvilla ◽  
Nishant Kumar Gupta ◽  
Anu Sebastian ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Dose Level ◽  
Chronic Toxicity ◽  
Withania Somnifera ◽  
Clinical Signs ◽  
Repeated Administration ◽  
Female Rats ◽  
Toxic Effects ◽  
Toxicity Studies ◽  
Adverse Effect Level

Objective: The objective of the present study was to evaluate the acute and sub-chronic (90 d; repeated dose) toxicity of Withania somnifera (ashwagandha) extract in rats.Methods: The acute toxicity was evaluated as per OECD (Organisation for Economic Co-operation and Development) guidelines 423. Purified ashwagandha extract (PAE) was fed at 2000 mg/kg body weight (bw) to overnight fasted female rats. The animals were observed daily for clinical signs of abnormality/mortality. After 14 d, animals were sacrificed and gross pathological changes were recorded. Sub-chronic toxicity of PAE was studied by feeding the extract at 100, 500 and 1000 mg/kg bw daily to rats as per OECD guidelines 408. After 90 d feeding, heamatological and biochemical parameters of treated rats were compared with control animals. Histopathology of all the major organs was also studied.Results: In the acute toxicity study, no mortality or clinical signs of toxicity were observed in any of the animals at maximum recommended dose level of 2000 mg/kg bw; therefore the LD50 is>2000 mg/kg bw in rats. The repeated administration of PAE for 90 d in rats at the maximum dose level of 1000 mg/kg bw did not induce any observable toxic effects, when compared to its corresponding control animals. The hematology and biochemistry profile of treated rats was similar to control animals and difference was non-significant (p>0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL (No Observed Adverse Effect Level) was calculated as 1000 mg/kg bw daily for rats.Conclusion: The present study clearly indicates that PAE does not have any toxic effects in animals at the dose evaluated as evidenced by acute and sub chronic toxicity studies in rats.

scholarly journals Influence of microbiological starter of filler of biofilter of "Filtronorm D" on stored of rainbow trout

2019 ◽  
pp. 15-21
Author(s):  
N. Grynevych
Keyword(s):  
Rainbow Trout ◽  
Clinical Signs ◽  
Aquatic Organisms ◽  
The Body ◽  
Toxic Effects ◽  
Long Time ◽  
Favorable Conditions ◽  
Experimental Group ◽  
Ultrasound Scanner ◽  
Brown Color

Creation in biofilters of favorable conditions for the existence of biocenoses secures RAS from the toxic effects of nitrites, which until recently did not attach great importance to toxicants for aquatic organisms. However, it has been found that they are very toxic to fish and aquatic invertebrates. The purpose of the work was to investigate the effect of microbiological starter of the "Filtronorm-D" biofilter filler on the behavior of adult rainbow trout during the launch of the biofilter. Investigation of the influence of the microbial starter of the filtrotorm-D biofilter filler on the behavior and clinical condition and the preservation of rainbow trout during the launch of the biofilter of the ultrasound has been studied. Evaluated the clinical signs of adult rainbow trout during the launch of the biofilter CWS for the use of polypropylene filler RK PLAST-control in it. According to the second variant, the clinical signs of adult rainbow trout were evaluated during the startup of the biofilter of the ultrasound scanner for the use of polypropylene filler RK PLAST in it and the addition of the microbiological starter of the biofilter "Filtronorm-D" – experiment. In the experimental group, the biofilter water was introduced by our microbiological starter, biofilter filler "Filtronorm-D", containing live cultures of nitrifying and denitrifying bacteria in the amount of 107 CFU/cm3. On the 10th day of the experiment, after the application of the microbiological starter of the biofilter filler "Filtronorm-D", approximately 5 % of the fish with the initial clinical signs of nitrite poisoning were detected. The fish for a long time stood motionless in the corners of the pool, they had the darkening of the body and the brown color of the gills. On the 15th day after the launch of the CWS and the use of "Filtronorm-D", changes in behavior were detected in most of the research objects, which may indicate an increase in the amount of nitrites in water and their effect on the body of trout. Approximately 25 % of fish for a long time stays motionless in the corners of the pool, the mobility of the whole fish has decreased, some individuals have risen to the surface of the water. Changes in pigmentation of the body were also found in approximately 10 % of the individuals. The body became darker, the fins were sealed, the gills got brown color. During this trial period, the mortality rate of the fish was 1,3 %. On the 20th day of the experiment, the signs of nitrite poisoning of fish became increasingly pronounced. Approximately 30 % of the fish showed the presence of darkening of the body and fins, the latter were sealed. In the same fish, the changed color of the gills was observed – from red to brown. In addition, during this period of research, the highest trout death was determined – 3,1 %, which is almost 2.4 times (p <0,05) higher than in the 15-day period. The period of ultrasound starting from the 20th to the 25th day was characterized by a decrease in the content of nitrites from 1,1 mg/dm3 to 0.6 mg/dm3. The process of reducing the content of nitrites in water affected the activity of fish – only about 20 % of trout swam in the upper layers of water. On the 30th day of the launch of the ultrasound with the use of the microbiological starter of the biofilter filler "Filtronorm-D" no signs of nitrite poisoning in rainbow trout were noted. The loss of fish in the indicated period was practically not marked. At the same time, during the application of polypropylene filler RK PLAST without the addition of a microbiological starter of the biofilter filler "Filtronorm D", the most problematic period for fish, in which it is most dying due to the effect of nitrites, is the period from 25 to 30 days. Thus, the conducted researches prove that during the launch of ultrasound for the use of polypropylene filler RK PLAST in it and the addition of the microbiological starter of the biofilter fillter "Filtertronorm D" the most dangerous is the period from 15 to 20 days. During this period, the largest death of fish and signs of nitrite poisoning is recorded, which requires the implementation of veterinary and sanitary preventive measures to reduce the toxic effects of nitrites. Key words: RAS, rainbow trout, biofilter, "Filtronorm-D", nitrites, fish behavior, signs of poisoning.

scholarly journals Single Oral Acute Toxicity of Banhasasim-Tang and Its Antiobesity Effect on Diet-Induced Obese Mice and 3T3-L1 Adipocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Soo-Jin Jeong ◽  
Mee-young Lee ◽  
Hyeun-Kyoo Shin ◽  
Chang-Seob Seo ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Acute Toxicity ◽  
Body Weight Gain ◽  
Clinical Signs ◽  
The Body ◽  
Dependent Manner ◽  
Obese Mice ◽  
Triglyceride Accumulation ◽  
Sd Rats

We had tested antiobesity effect of 52 traditional herbal formulas in 3T3-L1 adipocyte, and Banhasasim-tang (BHSST) was chosen as one of the effective medications to inhibit triglyceride accumulation. We investigated the antiobesity effect of BHSST on 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese mice. In addition, we evaluated the acute toxicity of BHSST in Sprague Dawley (SD) rats. Differentiated 3T3-L1 cells were treated with various concentrations of BHSST for 8 days. Accumulated triglyceride level and the expressions of adipogenesis-related genes and proteins were subsequently investigated. To evaluate the single oral toxicity of BHSST, the SD rats of each sex were administered a single dose (5000 mg/kg) of BHSST via oral gavage; the control group received vehicle only. After a single administration, the mortality, clinical signs, gross findings, and body weight were monitored for 15 days. Male C57BL/6J mice were fed HFD for 4 weeks to induce obesity and randomly received 50 mg/kg of Orlistat (n=12, OR), 200 mg/kg of BHSST (n=12, B200), and 1000 mg/kg of BHSST (n=12, B1000) for another 8 weeks. BHSST suppressed the triglyceride contents and lipid accumulation in a dose-dependent manner in 3T3-L1 adipocytes. BHSST also downregulated the adipogenesis-related gene levels and protein expression compared with those in undifferentiated adipocytes. In a single oral dose toxicity study, there was no adverse effect on mortality, clinical signs, body weight changes, and gross findings in the treatment group. HFD-fed mice treated with BHSST showed significantly reduced body weight gain, food efficiency ratio, and white adipose tissue weight. The medial lethal dose (LD50) of BHSST was 5000 mg/kg/day body weight for each sex in the rats. BHSST decreased the body weight gain in HFD-fed obese mice and inhibited triglyceride accumulation via a cascade of multiple factors at the mRNA and protein levels in 3T3-L1 adipocytes.

scholarly journals Modifying effect of triadimefon on the development of preneoplastic lesions and tumours in rat multi-organ carcinogenesis

2019 ◽  
Vol 84 (4) ◽  
pp. 5-18
Author(s):  
N.M. Nedopytanska ◽  
E.A. Bagley ◽  
O.V. Reshavska ◽  
V.S. Lisovska ◽  
L.V. Tkachenko
Keyword(s):  
Body Weight ◽  
Clinical Signs ◽  
The Body ◽  
Nitroso Compounds ◽  
High Dose ◽  
Environmental Carcinogens ◽  
Preneoplastic Lesions ◽  
Effect Level ◽  
Benign Tumours ◽  
Prostatic Gland

Throughout life, the human body is exposed to multiple environmental carcinogens that may stimulate carcinogenesis in different organs. Critical place among these carcinogens belongs to nitroso compounds. Triadimefon belongs to the chemical class of triazoles that are widely used as fungicides in pesticides and medicinal products. Objective is to investigate the effect of triadimefon on the development of preneoplastic lesions of the tissues and tumours in carcinogenesis induced in different organs by nitroso compounds. Materials and Methods. Experiments were performed in male Wistar Han rats in which nitroso compounds - N-nitrosodiethylamine, N-methylnitrosourea, N-nitrosobis(2-hydroxypropyl) amine induced multi-organ carcinogenesis according to the N.Ito. protocol. Triadimefon at the doses: 16.0 and 80.0 mg/kg body weight that corresponded to the no-observed-effect and observed effect level by carcinogenic effect were administered intragastrically on a daily basis for 20 weeks. Clinical studies were conducted throughout the experiment. The general condition of animals, their body weight and body weight gain were assessed. After necropsy, gross examination, including aberrant multiple crypts of the colonic mucosa, and histological examinations were conducted. Nodules positive for γ-glutamyl transpeptidase (γ-GTP) were determined by histochemistry in the hepatic tissue. Results. No clinical signs of toxic action of triadimefon in rat body induced by nitroso compounds to carcinogenesis were established. No specific organotrophic action of triadimefon was found by changes in the internal organ weight, except for liver. High dose resulted in the increase of liver weight, as well as in the number and size of γ-GTP positive nodules suggesting an increase in the pool of transformed hepatocytes. Histological examination of internal organs allowed detecting proliferative processes that are criterial markers of carcinogenicity of chemical substances upon their study in multi-organ model. The tendency to the increase in the rate of dose-dependent thyroid adenoma has been established. Increase in the rate of epithelium hyperplasia of oesophagus and forestomach, prostatic gland, as well as the total rate of benign tumours in different organs of animals on the tumour-inducing dose of triadimefon was found. The rate of malignancies in these animals do not differ from the control. Conclusion. The tumour-inducing dose of triadimefon shows weak promotor effect on the development of preneoplastic lesions of tissues of the thyroid gland, liver, oesophagus and forestomach, prostatic gland, as well as on the development of benign tumours in rats induced by carcinogenic nitroso compounds. No-observed-effect level of triadimefon by oncogenic effect established in chronic experiments ensures its safety upon exposure in the body of rats initiated by carcinogenic nitroso compounds. Regulations developed on this parameters ensure oncological safety of its use in human.

scholarly journals Acute and Subacute Oral Toxicity Assessment of European Cranberrybush (Viburnum opulus L). Fruit Extract

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 355-355
Author(s):  
Gizem Ozan ◽  
Alev Cumbul ◽  
Engin Sümer ◽  
Dilara Baban ◽  
Ahmet Aydın ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Toxicity Study ◽  
High Dose ◽  
Oral Toxicity ◽  
Viburnum Opulus ◽  
Fruit Extract ◽  
Subacute Toxicity

Abstract Objectives The intake of the high dose of polyphenols might cause adverse health effects on humans, in such cases, toxicological testing may be required to ensure safe levels of intake. In the present study, acute and subacute oral toxicity studies of polyphenol-rich European cranberrybush (Viburnum opulus L.) (ECB) fruit extract were evaluated to ensure the safe use of this extract. Methods In acute toxicity, freshly prepared ECB extract dissolved in distilled water was administrated to Sprague-Dawley rats by oral gavage at a single dose of 2000 mg/kg and signs of toxicity and mortality was observed. In subacute toxicity, Balb-c mice were administrated orally at 500 (low dose) and 2000 mg/kg (high dose) of ECB extract for 28 days and their mortality, clinical signs and, body weight were recorded on a daily and weekly basis, respectively. At the end of 28 days, while blood samples from each animal were taken for hematological and biochemical analysis, vital organs were taken for histopathological examination. Results In acute toxicity study, ECB extract showed no toxicological signs observed on behavioral change and body weight of rats after 14 days indicating that the lethal dose (LD50) of the ECB fruit extract might be higher than 2000 mg/kg. No death and no abnormal clinical signs were also recorded in subacute toxicity study. However, the increment in body weight of administrated high dose of ECB extract animals were significantly lower than control (P &gt; 0.05). High dose of ECB fruit extract induced the level of in some hematological parameters. Even amylase and lipase values were lower than normal ranges at high dose animals, other biochemical parameters results were not significantly different from the controls. In histopathological examination, the total histopathological scores ECB extract administrated mice at both doses were showed normal histological features in many tissues compared to control. However, administrated with a high dose of ECB extract showed significant changes in kidney, liver, and adipose tissue that were alterations (edema, infiltration, and bleeding) compared to control. Conclusions These findings indicated that polyphenol-rich ECB extract might show a toxic effect at a high dose (2000 mg/kg) and no observed adverse effect level (NOAEL) of ECB extract was 500 mg/kg ECB fruit juice. Funding Sources This study was supported by Yeditepe University.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

PHARMACOGNOSTIC, ANTIOXIDANT AND ACUTE TOXICITY STUDY OF Ficus sycomorus (Linn) (Moraceae) ROOT AND STEM BARK

2020 ◽  
Vol 4 (2) ◽  
pp. 605-614
Author(s):  
Murtala M. Namadina ◽  
H. Haruna ◽  
U. Sanusi
Keyword(s):  
Acute Toxicity ◽  
Radical Scavenging ◽  
Stem Bark ◽  
The Body ◽  
Toxicity Study ◽  
Bark Extract ◽  
Root Extract ◽  
Acute Toxicity Study ◽  
Radical Scavenging Ability ◽  
Phytochemical Components

Most of biochemical reactions in the body generates Reactive Oxygen Species (ROS), which are involved in the pathogenesis of oxidative stress-related disorders like diabetes, nephrotoxicity, cancer, cardiovascular disorders, inflammation and neurological disorders when they attack biochemical molecules like proteins, lipids and nucleic acid. Antioxidants are used to protect the cells or tissues against potential attack by ROS. Most medicinal plants possess a rich source of antioxidants such as flavonoids, phenols, tannins, alkaloids among others. These phytochemicals are currently pursued as an alternative and complimentary drug. In this study, phytochemical components, antioxidant and acute toxicity study of the methanol extract of stem bark and root of F. sycomorus were carried out using standard methods. Findings from this study revealed the presence of some diagnostic microscopical features such as calcium oxalate, starch, gum/mucilage, lignin, Aleurone grain, suberized/Cuticular cell wall and inulin but calcium carbonate was absent in stem bark but present in the powdered root. Quantitative physical constants include moisture contents (6.40% and 7.82%), ash value (7.20% and 9.30 %) in stem bark and root respectively. Carbohydrates, alkaloid, flavonoids, saponins, tannins, glycoside, steroid, triterpenes and phenols were present in all the extracts. They were found to exhibit potent 1,1,-diphenyl 2-picryl hydrazyl (DPPH) free scavenging activity. The DPPH radical scavenging ability of the extracts showed the following trend Ascorbic acid < stem bark extract˃ root extract. The LD50 of the methanolic stem bark and root extracts were found to be greater than 5000 mg /kg and is considered safe for use. Nonetheless, further

Comparison of search techniques (printed and computerised) with specific reference to the RTECS databank

1985 ◽  
Vol 10 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Anne Costigan ◽  
Frances E. Wood ◽  
David Bawden
Keyword(s):  
Computer System ◽  
Comparative Evaluation ◽  
Computer Systems ◽  
Toxic Effects ◽  
Specific Reference ◽  
Substructure Search ◽  
Search Techniques ◽  
General Relevance ◽  
Text Searching

A comparative evaluation of three implementations of a large databank, the NIOSH Registry of Toxic Effects of Chem ical Substances, has been carried out. The three implementa tions are: a printed index, a text searching computer system, and a computerised chemical databank system, with substruc ture searching facilities. Seven test queries were used, with the aim of drawing conclusions of general relevance to chemical databank searching. The computer systems were shown to have advantages over printed indexes for several of the queries, including those involving an element of browsing. Substructure search facilities were especially advantageous. Aspects of indexing of data present, and the criteria for inclusion of types of data, were also highlighted.

scholarly journals Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Josep Homedes ◽  
Marta Salichs ◽  
Antonio Guzman
Keyword(s):  
Safety Margin ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Clinical Pathology ◽  
Occult Blood ◽  
Study Groups ◽  
Placebo Control ◽  
Relevant Dose ◽  
Mucosal Bleeding ◽  
Animal Safety

Abstract Background Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. Results No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. Conclusions Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.

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