scholarly journals Study of the acute toxicity of the praziquantel using different routs of administration

2018 ◽  
pp. 91-96
Author(s):  
І. L. Kechin ◽  
D. M. Romanina ◽  
V. V. Gladishev ◽  
A. D. Dudun
Keyword(s):  
Acute Toxicity ◽  
Clinical Symptoms ◽  
Topical Administration ◽  
Rectal Administration ◽  
Negative Influence ◽  
Preclinical Study ◽  
Dosage Forms ◽  
White Rats ◽  
Rectal Suppository ◽  
Gastrointestinal Side Effects

Patients with similar to acne dermatosis have more strongly pronounced clinical symptoms and significant increase of relapses rate in case of the demodicosis presence. Praziquantel is an antiparasitic substance with activity regarding to flukes and cestodes. Investigations carried out by the domestic scientists exposed also a presence of the antidemodicosic effect. In Ukraine praziquantel is registered in the form of the oral tablets long using of which provokes gastrointestinal side effects. In view of this fact usage of alternative praziquantel routs of administration draws interest.  The aim of this work is study of the acute toxicity of the praziquantel using intraperitoneal, oral, rectal and topical administration. Investigations of the toxicity were carried out according to the order of preclinical study and data examination of the preclinical study of drugs. It was established that praziquantel intraperitoneal (LD50 = 564 mg/kg) and intragastric (LD50 = 1 030 mg/kg) administration in white rats by the extent of toxicity is a slightly dangerous substance (3 toxicity class). Study of the acute toxicity of the model semisolid application dosage forms in subtoxic dose for external administration showed that single applying of the external ointment and rectal suppository with this active substance in the maximum allowable volume doesn’t lead to the laboratory animal’s death and doesn’t negative influence on the examining parameters of their homeostasis. It is determined that praziquantel dosage forms for the external and rectal administration less toxic than oral tablets and are practically nontoxic substances.

scholarly journals Determination of acute toxicity parameters of the drug ‘MEGASTOP for dogs’ on white rats and mice

2020 ◽  
Vol 6 (2) ◽  
pp. 20-26
Author(s):  
O. L. Orobchenko ◽  
M. Ye. Romanko ◽  
M. O. Yaroshenko ◽  
I. O. Gerilovych ◽  
N. A. Zhukova ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Clinical Symptoms ◽  
Liver Volume ◽  
Male Rats ◽  
Toxic Substances ◽  
Main Experiment ◽  
Polyethylene Glycol 400 ◽  
White Rats ◽  
Rats And Mice

The experiments were performed on 58 males of nonlinear white rats 3–4 months old and weighing 180–200 g and 64 females of nonlinear white mice 2.5–3 months old and weighing 18–22 g. In the main experiment on rats, six experimental groups were formed, the animals of which were injected intragastrically with the drug ‘MEGASTOP for dogs’ (by absolute weight) in doses of 1,000.0, 2,000.0, 3,000.0, 4,000.0, 5,000.0, and 6,000.0 mg/kg body weight; in the main experiment on mice, seven experimental groups were formed, the animals of which were administered the drug in doses of 100.0, 500.0, 1,000.0, 1,500.0, 2,000.0, 2,500.0, and 3,000.0 mg/kg body weight. Control rats and mice were injected with 2.0 cm3 and 0.2 cm3 of polyethylene glycol-400, respectively. Clinical symptoms of poisoning with the drug ‘MEGASTOP for dogs’ of white rats (at doses of 2,000.0–6,000.0 mg/kg body weight) and mice (at doses of 1,000.0–3,000.0 mg/kg body weight) were refusals of food and water, loss of coordination, sitting in one place, a dose-dependent increase in depression with subsequent complete depression, lack of response to external stimuli and death on the first or fourth day after administration. During autopsy in rats and mice that died as a result of poisoning with the drug ‘MEGASTOP for dogs’, we recorded pallor of the mucous membranes of the mouth, trachea, pharynx, and esophagus; increase in heart volume, atrial blood supply; pulmonary hyperemia; uncoagulated blood; increase in liver volume, dark cherry color, flabby consistency; catarrhal inflammation of the mucous membrane of the small intestine. According to the results of determining the parameters of acute toxicity of the drug ‘MEGASTOP for dogs’ in the case of a single intragastric injection, LD50 for male rats is 3,384.98 ± 444.94 mg/kg, and for female mice — 2,025.88 ± 279.46 mg/kg body weight, which allows to classify it to class IV by the toxicity — low-toxic substances (LD50 — 501–5,000 mg/kg) and by the degree of danger to class III— moderately dangerous substances (LD50 — 151–5,000 mg/kg)

scholarly journals STUDY OF ACUTE TOXICITY OF A NEW VETERINARY DRUG FOR INTTRAMMARY INTRODUCTION

2018 ◽  
Vol 2 ◽  
pp. 51-60
Author(s):  
Zhanna Polova
Keyword(s):  
Acute Toxicity ◽  
Lethal Dose ◽  
Dosage Forms ◽  
Veterinary Drug ◽  
Test Substance ◽  
Medicinal Products ◽  
Preclinical Research ◽  
Toxic Compounds ◽  
White Rats ◽  
Veterinary Medicinal Products

Preclinical studies of veterinary medicinal products are important and compulsory studies in the development of new dosage forms. The aim of preclinical research is to determine the toxic effect and therapeutic efficacy of the test substance-the future dosage form, its effect on the body's basic systems, as well as the identification of possible side effects. This work is part of the research on the development of the composition and technology of the veterinary drug - a solution for intramammary application, conventionally called "Argocide", intended for the treatment of mastitis in cattle. A study of the acute toxicity of the intramammary veterinary drug was carried out in experiments on white rats of both sexes, according to the requirements for potential medicines. The establishment of the value of the average lethal dose (LD50) of the veterinary drug "Argocide" with intramuscular single administration to white mature rats is impossible due to the absence of animal death even when the drug is administered at doses exceeding 5.0 ml/kg. This experiment allows the veterinary preparation "Argocide" to be classified as practically non-toxic compounds (V class). The analysis of the results of the conducted studies indicates the relative harmlessness of the potential drug for veterinary medicine and allows us to foresee that the "Argocide" preparation can be classified as low-risk substances, which justifies the expediency of its further study and introduction into practice.

PRECLINICAL STUDY OF GENERAL TOXIC PROPERTIES OF THE TOOL Z-88 ON WHITE RATS

2020 ◽  
Vol 242 (2) ◽  
pp. 112-115
Author(s):  
F.A. Medetkhanov ◽  
◽  
V.G. Sofronov ◽  
E.K. Papunidi ◽  
M.I. Gilemkhanov ◽  
...  
Keyword(s):  
Preclinical Study ◽  
White Rats

scholarly journals SPIROCHÆTA MORSUS MURIS, N.SP., THE CAUSE OF RAT-BITE FEVER

1917 ◽  
Vol 25 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Kenzo Futaki ◽  
Itsuma Takaki ◽  
Tenji Taniguchi ◽  
Shimpachi Osumi
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Clinical Symptoms ◽  
Intermittent Fever ◽  
Lymph Glands ◽  
Short Forms ◽  
White Rats ◽  
Rat Bite Fever ◽  
Rats And Mice ◽  
Aniline Dyes

1. Since our first report on the discovery of the cause of rat-bite fever, we have been able to prove the existence of the same spirochete in five out of six more cases which have come under our observation. 2. The clinical symptoms of rat-bite fever are inflammation of the bitten parts, paroxysms of fever of the relapsing type, swelling of the lymph glands, and eruption of the skin, all occurring after an incubation period usually of from 10 to 22 days, or longer. 3. Our spirochete is present in the swollen local lesion of the skin and the enlarged lymph glands. But as the spirochetes are so few in number it is exceedingly difficult to discover them directly in material taken from patients. It is therefore better to inoculate the material into a mouse. In some cases the organism is found in the blood of the inoculated animal after a lapse of 5 to 14 days, or at the latest 4 weeks. 4. Generally speaking, the spirochetes present thick and short forms of about 2 to 5 µ and have flagella at both ends. Including the flagella, they measure 6 to 10 µ in length. Some forms in the cultures reach 12 to 19 µ excluding the flagella. The curves are regular, and the majority have one curve in 1 µ. Smaller ones are found in the blood and larger ones in the tissues. 5. The spirochetes stain easily. With Giemsa's stain they take a deep violet-red; they also stain with ordinary aniline dyes. The flagella, too, take Giemsa's stain. 6. The movements of our spirochetes are very rapid, resembling those of a vibrio, and distinguish them from all other kinds of spirochetes. When, however, the movements become a little sluggish, they begin to present movements characteristic of ordinary spirochetes. 7. For experimental purposes, mice, house rats, white rats, and monkeys are the most suitable animals. Monkeys have intermittent fever after infection, and spirochetes can be found in their blood, but they are not so numerous as in the blood of mice. Mice are the most suitable animals for these experiments, and they appear, as a rule, to escape fatal consequences. 8. The spirochete is markedly affected by salvarsan. 9. The organism is not present in the blood of all rats, and there is no relation between the species of the rat and the ratio of infection. We have never found the spirochete in healthy guinea pigs or mice. By permitting a rat infected with the spirochete to bite a guinea pig, the latter develops the disease. 10. We have succeeded in cultivating the spirochete in Shimamine's medium. 11. Among the spirochetes described in the literature or discovered in the blood of rats and mice, there may be some resembling our spirochete, but none of the descriptions agree with it fully. Hence we have named our organism Spirochæta morsus muris and regard it as belonging to the Spironemacea (Gross) of the nature of treponema. 12. The spirochete can be detected in the bodies of patients. In seven cases out of eight, it disappears on recovery, only to reappear during the relapse. 13. The spirochete can be detected in about 3 per cent of house rats. These facts enable us to identify the cause of the disease. 14. There may be other causes than the spirochete for diseases following the bite of a rat. The cause, however, of rat-bite fever in the form most common in Japan is, we believe, the spirochete which we have described.

scholarly journals Chamaejasmine Isolated from Wikstroemia dolichantha Diels Suppresses 2,4-Dinitrofluoro-benzene-Induced Atopic Dermatitis in SKH-1 Hairless Mice

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 697 ◽  
Author(s):  
Tae-Young Kim ◽  
No-June Park ◽  
Jonghwan Jegal ◽  
Sangho Choi ◽  
Sang Woo Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Symptoms ◽  
Skin Barrier ◽  
Topical Administration ◽  
Skin Lesions ◽  
Specific Ige ◽  
Transepidermal Water Loss ◽  
Skin Barrier Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dermal Thickness

Plants of the genus Wikstroemia have long been used as traditional medicines to treat diseases like pneumonia, rheumatism, and bronchitis. This study was designed to determine the effect of chamaejasmine, a biflavonoid present in W. dolichantha, on atopic dermatitis (AD)-like skin lesions in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD. Initially, we examined the anti-allergic activities of ten flavonoids from W. dolichantha by measuring β-hexosaminidase release from RBL-2H3 cells. Subsequently, an SKH-1 hairless mouse model of AD was developed based on the topical application of DNCB. Chamaejasmine (0.5%) or pimecrolimus (1%, positive control) were applied to dorsal skins of DNCB-sensitized AD mice for two weeks. Serum IL-4 and IgE levels were determined using enzyme-linked immunosorbent assay kits and transepidermal water loss (TEWL) and skin hydration were measured using a Tewameter TM210 and a SKIN-O-MAT, respectively. Of the ten flavonoids isolated from W. dolichantha, chamaejasmine most potently inhibited DNP-specific IgE-induced degranulation in RBL-2H3 cells. Topical administration of chamaejasmine attenuated the clinical symptoms of DNCB-induced dermatitis (i.e., itching, dryness, erythema, and edema). Histological analyses demonstrated that dermal thickness and mast cell infiltration in dermis were significantly reduced by chamaejasmine. In addition, 0.5% chamaejasmine inhibited DNCB-induced increases in total IL-4 and IgE levels in serum, improved skin barrier function, and increased epidermis moisture. Our findings suggest chamaejasmine might be an effective therapeutic agent for the treatment of atopic diseases.

scholarly journals Clearance of Escherichia coli O157:H7 Infection in Calves by Rectal Administration of Bovine Lactoferrin

2014 ◽  
Vol 81 (5) ◽  
pp. 1644-1651 ◽  
Author(s):  
E. Kieckens ◽  
J. Rybarczyk ◽  
L. De Zutter ◽  
L. Duchateau ◽  
D. Vanrompay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clinical Symptoms ◽  
Oral Treatment ◽  
Experimental Treatment ◽  
Rectal Administration ◽  
Fecal Excretion ◽  
Severe Illness ◽  
Control Group ◽  
Bovine Lactoferrin ◽  
Content Type

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) strains, of whichE. coliO157:H7 is the best-studied serotype, are an important group of foodborne pathogens causing severe illness in humans worldwide. The main reservoirs for EHEC are ruminants, mostly cattle, which harbor the bacteria in their intestinal tracts without showing clinical symptoms. In this study, we used bovine lactoferrin, a natural occurring bactericidal and immunomodulating protein, as an antibacterial agent against EHEC infection in cattle. Nine 3-month-old Holstein-Friesian calves were experimentally infected with EHEC (strain NCTC12900). Three animals received a daily rectal spray treatment with bovine lactoferrin, three animals received an oral treatment, and three animals served as a control group. Blood samples were collected weekly and fecal samples twice weekly to monitor antibody responses and fecal excretion, respectively. Animals in the rectal group ceased shedding within 26 days of the experimental treatment and remained negative. This beneficial effect of bovine lactoferrin was not observed in the oral group, where animals were still shedding at the time of euthanasia (day 61). All groups developed serum responses, but no clear differences could be observed between the groups. However, the results indicate that the use of bovine lactoferrin as a rectal treatment can be a useful strategy to preclude further transmission of EHEC infections from cattle to humans.

scholarly journals Phytochemical Identification, Acute, and Sub-Acute Oral Toxicity Studies of the Foliar Extract of Withania frutescens

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4528 ◽  
Author(s):  
Abdelfattah EL Moussaoui ◽  
Mohammed Bourhia ◽  
Fatima Zahra Jawhari ◽  
Hamza Mechchate ◽  
Meryem Slighoua ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Clinical Symptoms ◽  
Ethanolic Extract ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Oral Toxicity ◽  
Phytochemical Composition ◽  
Subacute Toxicity ◽  
Repeated Doses

Withania frutescens (W. frutescens) is a medicinal plant widely used to treat several diseases. This work aims to study phytochemical composition as well as acute and subacute toxicity of W. frutescens hydroethanolic extract in mice. The phytochemical composition of W. frutescens extract was performed using gas chromatographic analysis. Acute toxicity was studied in vivo with oral administration of single doses 400 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was studied with the administration of repeated doses of 400 mg/kg/day and 2000 mg/kg/day for 28 days. Phytochemical analysis of W. frutescens hydro-ethanolic extract confirmed the presence of interesting chemical compounds. Acute toxicity results showed no toxic symptoms in mice treated with an increasing dose up to a maximum of 2000 mg/kg. Alongside acute toxicity, subacute data showed no clinical symptoms nor biochemical or histological alteration in mice treated with an increasing dose up to a maximum of 2000 mg/kg compared to the control group (p < 0.05). This study shows no toxic effects in animals treated with W. frutescens extract, and, therefore, this plant can be considered safe in animals up to 2000 mg/kg under both acute and subacute toxicity conditions.

scholarly journals Effects of Standardised Fermented Papaya Gel on Clinical Symptoms, Inflammatory Cytokines, and Nitric Oxide Metabolites in Patients with Chronic Periodontitis: An Open Randomised Clinical Study

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Zaira F. Kharaeva ◽  
Lyana R. Zhanimova ◽  
Magomet Sh. Mustafaev ◽  
Chiara De Luca ◽  
Wolfgang Mayer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gingival Crevicular Fluid ◽  
Clinical Symptoms ◽  
Topical Administration ◽  
Control Group ◽  
Pocket Depth ◽  
Bacterial Killing ◽  
Anti Inflammatory ◽  
Nitric Oxide Metabolites ◽  
Crevicular Fluid

The clinical efficacy of topical administration of standardised fermented papaya gel (SFPG), known to have antioxidant and anti-inflammatory properties,versusconventional therapy was evaluated in a group of 84 patients with moderate-to-severe periodontitis, randomly assigned to control group (n=45) undergoing traditional pharmacologic/surgical protocols or to experimental group (n=39), additionally treated with intragingival pocket SFPG (7 g) applications (15 min daily for 10 days). Patients undergoing SFPG treatment showed significant (P<0.05), durable improvement of three major clinical indices of disease severity: reduced bleeding (day 7), plaque and gingival conditions (day 14), and consistent gingival pocket depth reduction (day 45). Proinflammatory nitric oxide metabolites reached normal values in plasma (day 14) and gingival crevicular fluid (GCF) at day 45 with SFPG applications compared to controls that did not reach normalisation. Levels of highly increased proinflammatory (IL-1B, IL-6) and suppressed anti-inflammatory (IL-10) cytokines normalised in the SFPG group by days 14 (plasma) and 45 (GCF), but never in the control group. Although not acting directly as antibiotic, SFPG acted in synergy with human granulocytes blocking adaptive catalase induction inS. aureusin response to granulocyte-derived oxidative stress, thus enhancing intracellular bacterial killing.

scholarly journals ESTIMATION OF REPRODUCTIVE TOXICITY OF THE COMPLEX PLANT REMEDY �TIREOTON�

2016 ◽  
Vol 1 (2) ◽  
pp. 0-0
Author(s):  
������ ◽  
Iraida Ubeeva ◽  
�������� ◽  
Sergey Nikolaev ◽  
��������� ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Wistar Rats ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Negative Influence ◽  
Laboratory Animals ◽  
White Rats ◽  
Embryo Toxicity ◽  
Probable Occurrence

To study the probable negative influence of the complex remedy �Tireoton� on the reproductive function of the laboratory animals the following tests have been carried out, namely the probable occurrence of embryo-toxicity, teratogenicity, foetotoxicity and its influence on the postnatal development of the laboratory animals progeny. The experiments have been carried out of the white Wistar rats. It has been established that the �Tireoton� at the doses of 75 and 750 mg/ kg has no embryotoxic, teratogenic and fetotoxical effect. The introduction of the �Tireoton� at the dose of 750 mg/kg since 6th to 19th day of pregnancy does not influence on the postnatal development of white rats progeny.

scholarly journals Evolution of Nanotechnology in Delivering Drugs to Eyes, Skin and Wounds via Topical Route

2020 ◽  
Vol 13 (8) ◽  
pp. 167 ◽  
Author(s):  
Pratheeksha Koppa Raghu ◽  
Kuldeep K. Bansal ◽  
Pradip Thakor ◽  
Valamla Bhavana ◽  
Jitender Madan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Wound Healing ◽  
Drug Delivery Systems ◽  
Complex Structure ◽  
Topical Administration ◽  
Dosage Forms ◽  
Improve Patient Compliance ◽  
Improve Patient ◽  
Drug Localization ◽  
Exogenous Substances

The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated with complications like intravitreal hemorrhage, retinal detachment, endophthalmitis, and cataracts. The skin has a complex structure that serves as numerous physiological barriers to the entry of exogenous substances. Drug localization is an important aspect of some dermal diseases and requires directed delivery of the active substance to the diseased cells, which is challenging with current approaches. Existing therapies used for wound healing are costly, and they involve long-lasting treatments with 70% chance of recurrence of ulcers. Nanotechnology is a novel and highly potential technology for designing formulations that would improve the efficiency of delivering drugs via the topical route. This review involves a discussion about how nanotechnology-driven drug delivery systems have evolved, and their potential in overcoming the natural barriers for delivering drugs to eyes, skin and wounds.

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