Acute and subacute toxicity of the drug based on tylosin tartrate

The article presents the results of a study of the acute and subacute toxicity of the drug TILOTAR (a water-soluble powder for oral administration) made on the basis of tilmicosin. As a result of the research it was found that the drug “TILOTAR” refers to the 4th class of toxicity, that is, to low-toxic substances. After intragastric administration of the drug to white mice and rats at doses of 2500, 5000, 7500 mg/kg, all animals remained alive. Short-term inhibition was recorded in laboratory animals, which were given the drug at the maximum dose. Further changes in the clinical state of the animals of the experimental groups were not observed. The study of subacute toxicity of the drug “TILOTAR” showed that 14-day administration of a therapeutic dose of the drug leads to a decrease in erythropoiesis, the appearance of old forms of erythrocytes, damage to hepatocytes, the appearance of eosinophils, γ-globulins, a decrease in protein biosynthesis, increased kidney function. The introduction of a 10-fold dose within 14 days reduced the body weight of the rats, leading to abnormalities in the liver and kidneys, and a decrease in the mass of the spleen. An increase in urea blood concentration and a decrease in creatinine may indicate impaired renal function in animals that were given a tenfold dose of the drug, and an increase in the level of α- and γ-globulins against the background of a decrease in body weight of rats indicates an overload of the body’s immune system. In rats of the therapeutic group, homeostasis was maintained by enhancing kidney function, accompanied by a decrease in the number of erythrocytes due to young forms and the appearance of mature erythrocytes with a high level of hemoglobin (MCH), some destruction of hepatocytes (high level of alkaline phosphatase activity) while reducing the amount of albumin, an increase in relative levels of α- and γ-globulins. In the conducted experiments it was established that the macroscopic and microscopic structure of the internal organs of rats, while studying the subacute toxicity of the drug “TILOTAR”, was preserved, no macroscopic changes were revealed. In rats receiving a 10-fold therapeutic dose of the drug for 14 days, focal protein dystrophy of the liver and kidneys was histologically established.

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Curcumin ameliorates atrophy of seminal vesicle via reduction of oxidative stress in castrated mice

PeerJ ◽

10.7717/peerj.7192 ◽

2019 ◽

Vol 7 ◽

pp. e7192 ◽

Cited By ~ 2

Author(s):

Rui Li ◽

Hao Li ◽

Ke Rao ◽

Kang Liu ◽

Yan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Seminal Vesicle ◽

Serum Testosterone ◽

The Body ◽

Intragastric Administration ◽

Curcumin Treatment ◽

Seminal Vesicle Weight ◽

High Level ◽

And Function

Background The growth and function of seminal vesicle are dependent on androgen. This study was conducted to investigate the role of oxidative stress in castration-induced seminal vesicle atrophy and to explore the effects of curcumin, an antioxidant extracted from rhizome of turmeric, on seminal vesicle of castrated mice. Methods C57BL/6J mice were randomly divided into three groups: control, castration, and castration with curcumin (n = 10 for each group). After surgical castration, mice in the curcumin treatment group received intragastric administration of curcumin at 100 mg/kg body weight for 4 weeks, whereas mice in the other two groups were treated with olive oil. After that, the body weight, seminal vesicle weight and serum testosterone of mice were measured. Apoptosis and oxidative stress levels in seminal vesicle were also determined. Results After castration, both the weight and size of seminal vesicle decreased dramatically. The expression of three NADPH oxidase (NOX) subtypes: NOX1, NOX2 and NOX4, increased in seminal vesicle of castrated mice, resulting in high level oxidative stress. The ratio of Bax to Bcl-2 was also elevated after castration, accompanied by enhanced caspase3 activity. Additionally, castration increased the number of apoptotic cells in seminal vesicle. Curcumin treatment could inhibit the expression of NOX1, NOX2 and NOX4, decreasing oxidative stress and apoptosis. The atrophy of seminal vesicle caused by castration was ameliorated by curcumin. Conclusion Castration could cause atrophy of seminal vesicle probably via inducing oxidative stress. Curcumin treatment could reduce the oxidative stress in seminal vesicle by decreasing the expression of NOX1, NOX2 and NOX4, thereby ameliorating apoptosis and atrophy of seminal vesicle. Oxidative stress might play a role in castration-induced seminal vesicle atrophy.

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Prosthesis Design for Bilateral Hip Disarticulation Management

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.664.423 ◽

2014 ◽

Vol 664 ◽

pp. 423-428

Author(s):

Mauricio Plaza Torres ◽

William Aperador

Keyword(s):

Body Weight ◽

Lower Extremity ◽

Hip Joint ◽

Joint Capsule ◽

The Body ◽

Body Weight Support ◽

Patient Mobility ◽

Weight Support ◽

Crush Injuries ◽

High Level

Hip disarticulation is an amputation through the hip joint capsule, removing the entire lower extremity, with closure of the remaining musculature over the exposed acetabulum. Tumors of the distal and proximal femur were treated by total femur resection; a hip disarticulation sometimes is performance for massive trauma with crush injuries to the lower extremity. This article discusses the design a system for rehabilitation of a patient with bilateral hip disarticulations. The prosthetics designed allowed the patient to do natural gait suspended between parallel articulate crutches with the body weight support between the crutches. The care of this patient was a challenge due to bilateral amputations at such a high level and the special needs of a patient mobility.

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Preclinical evaluation of the veterinary drug “Amoxidev 15” for its use in surgical and obstetric practice

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.32718/nvlvet10315 ◽

2021 ◽

Vol 23 (103) ◽

pp. 109-115

Author(s):

L.-M. Kostyshyn ◽

R. Sachuk ◽

Ye. Kostyshyn ◽

O. Katsaraba

Keyword(s):

Body Weight ◽

Soft Tissues ◽

Control Level ◽

Subcutaneous Administration ◽

The Body ◽

Laboratory Animals ◽

Veterinary Drug ◽

Intragastric Administration ◽

Toxicological Evaluation ◽

White Rats

Suspension for injection “Amoxidev 15” is prescribed to fur-bearing animals (mink, fox), dogs and cats for the treatment of respiratory diseases (tonsillitis, tracheitis, pneumonia, bronchitis, rhinitis, sinusitis, bronchopneumonia), digestive (gastritis, enteritis, enteritis). genitourinary systems (nephritis, urethritis, urocystitis, mastitis, metritis, agalactia), musculoskeletal system (arthritis, osteoarthritis, joint injuries, tendonitis, hoof lesions), skin and soft tissues (eczema, dermatitis) caused by sensitive drug by microorganisms, including colibacillosis, streptococcus, bronchopneumonia, etc. Toxicological evaluation of the veterinary drug “Amoxidev 15” under the conditions of acute and subacute toxicological experiments on a model of white rats. According to the results of an acute toxicological experiment with intragastric administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration. The maximum administered dose (in absolute weight of the drug) was 20000.0 mg/kg body weight, which allows to refer the drug to class VI toxicity of relatively harmless substances (DL50 > 15000 mg/kg body weight), and the degree of safety to class IV – low-hazard substances (DL50 > 5000 mg/kg). According to the results of an acute toxicological experiment with subcutaneous administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration, the maximum dose was 5000.0 mg/kg body weight, therefore, the drug “Amoxidev 15” when administered subcutaneously by toxicity can be classified as class VI substances relatively harmless (DL50 Subcut > 4500.0 mg/kg). When administered subcutaneously to white rats, the drug “Amoxidev 15” under conditions of subacute toxicological experiment in doses of 0.1–1.0 ml/kg does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, although 3-day administration of the drug in a dose 1.0 ml/kg body weight caused an increase in the activity of hepatospecific enzymes ALT and AST by 12.5 and 11.1 % (P < 0.05), respectively, relative to the control, which was restored to the control level 7 days after cessation.

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Evaluation of Anti-Obesity Activity, Acute Toxicity, and Subacute Toxicity of Probiotic Dark Tea

Biomolecules ◽

10.3390/biom8040099 ◽

2018 ◽

Vol 8 (4) ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Wang Ling ◽

Shungeng Li ◽

Xingcai Zhang ◽

Yongquan Xu ◽

Ying Gao ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Metabolic Disorders ◽

The Body ◽

High Fat ◽

Water Group ◽

Subacute Toxicity ◽

Infusion Group ◽

Sd Rats ◽

Group Ii

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.

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Prophylactic effect of vitamin E against hepatotoxicity, nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

Current Zoology ◽

10.1093/czoolo/55.3.219 ◽

2009 ◽

Vol 55 (3) ◽

pp. 219-226 ◽

Cited By ~ 11

Author(s):

Nahla S. El-Shenawy ◽

Rasha A. Al-Eisa ◽

Fawzia El-Salmy ◽

Omema Salah

Keyword(s):

Body Weight ◽

Vitamin E ◽

Kidney Function ◽

Kidney Tissue ◽

The Body ◽

High Dose ◽

Protective Effects ◽

Histopathological Changes ◽

Liver And Kidney ◽

Haematological Indices

Abstract Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight) on mice (25 - 30 mg) treated with diazinon (32.5 or 16.25 mg/kg body weight) organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE) were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), alkaline phosphatise (AIP), and some parameters of kidney function (urea and creatinine) in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH) decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE + DZN treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function.

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Changes in proteome profiles of rat liver microsomes induced by silicon dioxide nanoparticles

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20156101092 ◽

2015 ◽

Vol 61 (1) ◽

pp. 92-98

Author(s):

O.N. Tananova ◽

E.A. Arianova ◽

I.V. Gmoshinskii ◽

I.Yu. Toropygin ◽

E.V. Khryapova ◽

...

Keyword(s):

Mass Spectrometry ◽

Body Weight ◽

Liver Microsomes ◽

The Body ◽

Mass Spectrometry Analysis ◽

Control Group ◽

Intragastric Administration ◽

2D Electrophoresis ◽

Rat Liver Microsomes ◽

Mass Spectrometry Identification

The effect of daily intragastric administration of an aqueous dispersion of silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body weight for 28 days) to rats on the proteomic profile of liver microsomes has been investigated by 2D-electrophoresis followed by subsequent mass spectrometry identification. The liver microsomal fraction was isolated by differential centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel electrophoresis. Identification of protein spots was carried out using MALDI-TOF mass spectrometric analysis. The mass spectrometry analysis revealed the protein GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of heat shock proteins. This protein present in animals of the control group was not detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10 mg/kg body weight/day). This protein predominantly localized in the liver cell endoplasmic reticulum and plasma membrane has the chaperone biological activity. Possible mechanisms of the effects of engineered nanoparticles on biosynthetic processes in the body are discussed.

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Acute and subacute toxicity tests of goat bile in BALB/c mice

Veterinary World ◽

10.14202/vetworld.2020.515-520 ◽

2020 ◽

Vol 13 (3) ◽

pp. 515-520

Author(s):

Heny Arwati ◽

Windya T. Hapsari ◽

Kartika A. Wardhani ◽

Kholida N. Aini ◽

Ramadhani R. Bahalwan ◽

...

Keyword(s):

Body Weight ◽

Toxicity Test ◽

Harmful Effect ◽

Negative Control ◽

The Body ◽

Toxicity Tests ◽

Slight Reduction ◽

Subacute Toxicity ◽

Liver And Kidney ◽

Hematology Parameters

Aim: The aim of this study was to investigate the toxicity of goat bile in BALB/c mice since some Indonesian people consume raw goat gallbladder to treat malaria and increase stamina. Materials and Methods: Acute toxicity test was done in six groups of BALB/c mice using 100%, 50%, 25%, 12.5%, and 6.75% of goat bile and negative control. The death of mice was observed within 14 days. In the subacute toxicity test, the body weight and hematology parameters on day 0 and day 4 post-treatment were evaluated. The mice were closely observed for 28 days before plasma collection for the blood biochemistry evaluation. Results: Mild diarrhea was observed in acute and subacute toxicity tests. No death of mice was observed in acute test. Goat bile did not inhibit the increase of the body weight of mice. A slight reduction in hemoglobin and hematocrit levels in mice treated with 25% and 50% goat bile, however, remained normal in mice treated with 100% goat bile. The red and white blood cell count were not affected. Liver and kidney functions were not affected by goat bile treatment as revealed by the plasma level of aspartate aminotransferase and alanine aminotransferase, blood urea nitrogen, and creatinine, which remained in the normal range. Conclusion: Goat bile treatment in BALB/c mice caused mild toxicity in mice. Hydrophobic bile acids may cause the toxicity of goat bile in mice; therefore, it is recommended that goat bile consumption not to be taken oftenly to avoid its harmful effect.

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The study on tolerability and efficacy of the new complex drug «Helmintal tablets» based on moxidectin and praziquantel

Russian Journal of Parasitology ◽

10.12737/21664 ◽

2016 ◽

Vol 3 (3) ◽

pp. 403-408

Author(s):

Степанов ◽

V. Stepanov ◽

Арисова ◽

G. Arisova ◽

Смирнова ◽

...

Keyword(s):

Body Weight ◽

Body Temperature ◽

Body Mass ◽

Therapeutic Dose ◽

Biochemical Parameters ◽

Drug Efficacy ◽

The Body ◽

Before And After ◽

And Control ◽

Complex Drug

Objective of research: the study on tolerability and therapeutic efficacy of the complex drug Helmintal produced on the basis of two ingredients moxidectin and praziquantel. Materials and methods: In our research, we used four drug modifications: for cats and kittens weighting less than 4 kg (moxidectin 0.4 mg and praziquantel 10 mg); for cats — more than 4 kg (moxidectin 1.6 mg and praziquantel 40 mg); for dogs and puppies — less than 10 kg (moxidectin 1 mg and praziquantel 25 mg); for dogs — more than 10 kg (moxidectin 5 mg and praziquantel 125 mg.) To study the effect of the drug on the organism, three groups of clinically healthy animals were formed (5 animals per group): dogs 1 — 2 years of age with the body mass 18 — 20 kg; puppies 3 — 5 weeks of age weighting 0.8 — 1 kg; cats 1 — 2 years of age weighting 3 — 5 kg; kittens 6 — 8 weeks of age with the body mass 0.6 — 0.8 kg. The drug was given to animals orally once a day in the morning within 7 days in the following doses: the first experimental group — 0.4 mg moxidectin and praziquantel 10 mg per 1 kg of body weight (double therapeutic dose); the second group — moxidectin 1.0 mg and praziquantel 25 mg per 1 kg of body weight (five-fold therapeutic dose); the third group served as controls — the drug was not used. During the experiment, animals were monitored daily, their general health status, behavior, appetite were observed, weight and body temperature controlled. Before and 15 and 30 days after the beginning of the drug taking, several morphological and biochemical parameters of blood and urine were investigated. The study of the anthelmintic efficacy of the drug was carried out on the basis of veterinary clinics in Moscow and Moscow region. Altogether 205 cats and 209 dogs spontaneously infected were chosen for the experiment. The diagnosis and the drug efficacy were confirmed based on the clinical picture and on Fulleborn’s method used for detection of helminth eggs in animal’s feces followed by differentiation. Results and discussion: During the study on the drug tolerance it was found that the general status, mass and the body temperature of animals from experimental groups did not significantly differ from controls. Morphological and biochemical parameters of blood and urine in all animals from experimental and control groups did not differ significantly and were within the physiological norm before and after treatment. Thus, the research allows to conclude that the drug applied within 7 days at double and fivefold therapeutic doses has no adverse effect on dogs, puppies, cats and kittens. Most sick animals used in the experiment on the effectiveness of the drug, were emaciated, listless, their fur was ruffled, mucous membranes were pale; they suffered from anal itching, diarrhea and fecal retention. The drug was given after diagnosis; many dogs and cats ate it themselves, and other had no problems with eating pills due to their small size and pleasant taste. When applying the drug and throughout the experiment, no side effects and complications were observed in all animals. 10 and 20 days after giving the drug, its efficacy in the treatment of nematodosis and cestodosis of adult dogs cats as well as kittens and puppies was 100%.

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Neurotoxicity and Toxicokinetics of Artelinic Acid Following Repeated Oral Administration in Rats

International Journal of Toxicology ◽

10.1080/10915810701582913 ◽

2007 ◽

Vol 26 (5) ◽

pp. 401-410 ◽

Cited By ~ 13

Author(s):

Yuanzheng Si ◽

Qigui Li ◽

Lisa Xie ◽

Kent Bennett ◽

Peter J. Weina ◽

...

Keyword(s):

Body Weight ◽

Exposure Time ◽

Drug Exposure ◽

Neuronal Degeneration ◽

Neuronal Damage ◽

Dose Range ◽

Volume Of Distribution ◽

The Body ◽

Water Soluble ◽

Dosing Regimens

Neurotoxicity secondary to oil-soluble artemisinins has been reported in various animal species. The onset of neurotoxicity and toxicokinetics of oral artelinic acid (AL), a water-soluble artemisinin, were investigated. After dose range study, rats were dosed at either 160 mg/kg daily for 9 consecutive days or at 288 mg/kg once every other day for five doses, so that the total dose (1440 mg/kg) and duration (9 days) were identical. Neuronal damage of varying severity was identified beginning as early as 1 day after completing dosing and continued for up to 10 days post dosing. Neuronal injury was most severe 7 days after the last treatment in each of the two dosing regimens. The rats dosed with 160 mg/kg of AL daily showed moderate neurotoxicity and lost 22% of their body weight during treatment. Compared with the first dose, the toxicokinetic profile of this regimen changed significantly, with the elimination half-life increasing 3.82-fold and the volume of distribution increasing 5.23-fold on the last day of dosing. In the animals treated with AL at 288 mg/kg every other day for 5 doses, minimal neuronal degeneration (severity score 1.17) was identified and the body weight was only 8% loss. Furthermore, there were no obvious differences in the pharniacokinetic parameters between first and last dosing days with this regimen. Additionally, a progressively drug retention in stomach and drug accretion in blood were only found in rats treated with 160 mg/kg daily for 9 days. These results imply that delayed gastric emptying resulted in AL accumulation in blood and prolonged a neurotoxic exposure time (186 h) in 160 mg/kg rats when compared to that (75 h) in 288 mg/kg animals. Therefore, the drug exposure time is a key factor in the neurotoxicity induced by AL.

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Toxicological characteristics of the preparation FORTICEPTTM Hoof Oinment

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.32718/nvlvet9224 ◽

2018 ◽

Vol 20 (92) ◽

pp. 117-120

Author(s):

V. D. Ishchenko ◽

A. M. Shevchenko ◽

N. M. Slobodyuk ◽

R. O. Vasiv ◽

H. V. Yarova ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

The Body ◽

Average Weight ◽

Intragastric Administration ◽

Laboratory Mice ◽

White Rats ◽

Medicinal Preparations ◽

Medicinal Substances

Antibiotic resistance of the main infectious disease pathogens is one of the biggest problems of present time, which causes the need for searching for new antimicrobial medicinal substances and developing effective medicinal agents. One of the innovative medicinal preparations with the antimicrobial action, which is recommended for application for animals with hoof diseases, is ForticeptTM Hoof Oinment. Integration in the practice new medicinal preparations needs their strict toxicological control, which involves the exploring of acute and chronic toxicity and remote effects of possible side effect. The purpose of work was the determination of the acute toxicity parameters of the ForticeptTM Hoof Oinmentduring the oral administration to white laboratory mice and evaluation of the skin resorptive action of the preparation after it was administrated on rats’ skin. For determination of the acute toxicity there were used male laboratory mice with the average weight of the body 20 g – two groups with 10 animals in each. For the first group (the control one) with the help of the probe there was injected the distilled water (0.1 ml) into stomach. For the second group there was injected ForticeptTM Hoof Oinment (0.1 g), where the dose of the preparation is equal 500 mg/kg. For evaluation of the skin resorptive action of the preparation there were used 6 white rats with the average weight of the body 175 g. On the pre-prepared patch of skin there was administrated the preparation in the number that is equal 2857 mg/kg of body weight. For control there was leaved a free from preparation patch of bare skin. Exposition lasted for 4 hours. The indicators were explored in dynamics after 6, 24, 48 hours from the exposition started. After the research results there was established that ForticeptTM Hoof Oinment doesn’t cause death after its intragastric administration to the white laboratory mice in the number that is equal 5000 mg/kg of the body weight, that’s why depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). After one-time application of the preparation to the white rats in the number which is equal 2857 mg/kg of the body weight there wasn’t observes no death or pronounced changes in the behavior reactions, motor activity, state of the nervous system, amount of the consumed food and water. Therefore ForticeptTM Hoof Oinmentaccording to the results of the determination of the acute toxicity after its administration on the skin to the white rats depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). ForticeptTM Hoof Oinment doesn’t detect skin resorptive action, that points on the absence of toxic effects of the preparation due to its application on the skin.

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