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Objective To evaluate the safety of fibrin sealant (FS) intraperitoneal injection in SD rats .Methods 80 male and female SD rats were randomly divided into four groups (0 ,85.5 ,171 .0 ,342 .0 mg/kg) by body weight .All rats were in-traperitoneally injected with vehicle or FS daily for 14 days followed by a 28-day recovery period .The clinical signs ,hematolog-ical and biochemical indices were measured .The pathology were observed .Results Increase of white blood cell count (WBC) and decrease of fibrinogen (FIB) in d 14 were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Furthermore ,the tend-ency of weight increase of spleen were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Pathological exams of peritoneal cavity found that there were granulation tissues containing FS in some of the rats in 342 .0 mg/kg group .All of these changes got reversed after the recovery period .Conclusion The safety dose in this study is considered to be 85.5 mg/kg ,and the toxic-ity dose is 171 .0 mg/kg .The target toxicity systems or site of FS in SD rats are hematological system ,immune system and in-jection site .The toxic effects of FS are reversible .
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The quality management of drug research,development,registration,production and marketing strengthened by good practice for pharmaceuticals ensure the drag safety,effectiveness and quality control.Teaching of new drug research and evaluation in compliance with good practice for pharmaceuticals will be of value in making teaching content close to actual work,extending the students'knowledge and training student's good habits in scientific study.
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BACKGROUND: Besides being a basic growth factor crucial to maintain and promote the development, differentiation and survival of the central nervous system, nerve growth factor(NGF) also plays an important role in the repair of injured peripheral nerves.OBJECTIVE: To investigate the effect of the muscular injection of NGF on the regeneration and functional recovery of rat sciatic nerve after crush injury.DESIGN: A randomized controlled pilot study in rats with repeated observation and measurement.SETTING: Center for new drug evaluation in a military medical university.MATERIALS: This study was performed in the Center for New Drug Evaluation, Department of Basic Medicine, Second Military Medical University during the period from July 1999 to March 2000, using 40 SD rats weighing 200 to 250 g(of either sex of half number) provided by the Sino-British SIPPR/BK Lab Aninal Ltd (Shanghai).METHODS: Forty rats were randomized into high-, mid- and low-dose NGF treatment groups, normal control group and model control group. The sciatic nerves were clamped at 6 nm distal to the sciatic notch to induce a 4-mm-wide area of crush injury. In the high-, mid-; and low-dose NGF groups, the rats were given NGF at 8, 4 and 2 μg/kg per day(corresponding to 1.6 × 10 3, 8 × 10 2 and 4 × 10 2 IU/kg per day) respectively via the muscular injection for 56 consecutive days.(NCVs) and sciatic function index(SFI) at different time points after the RESULTS: Compared with that of the model control group, the NCVs significantly increased in the high-dose NGF group 35 and 56 days after the injury,and in the mid-dose NGFgroup at 35 days(t=2.32-5.14, P ＜0.05-0.01 ). The SFIs significantly increased in all NGF-treated groups at 14 days ( t = 2. 29-6.28, P ＜ 0.05-0.01 ), with the recovery most conspicuous in high-dose NGF group; No significant difference in the SFIs was found between the NGF-treated groups on the 56th day. Morphological examination of the tissues identified no significant difference in the nerve myelin sheaths and axons in NGF-treated groups as compared with the normal control group,while in the model control group, myelin sheath dislocation with unclear microstructure was observed, accompanied by Schwann cell degeneration and necrosis.CONCLUSION: NGF promotes the repair of the damaged nerve myelin sheath and axon and stimulates nerve fiber regeneration and function recovery of the crushed rat sciatic nerves.
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Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.
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Shiwei Dangguiyin(SWDGY)is mainly composed of Radix Angelicae Sinensis,Radix Adenophorae,Radix Notogenseng,Radix Bupleuri,etc. Oral administration of SWDGY could significantly inhibit the metatarsal swell- ing eaused by dimethylbenzene in rats,raise the pain threshold in hot-plate test and depress the torsive reaction caused by acetic acid in mice.In vitro SWDGY exerted bacteriostatic and bacteriocidal effects on Staphylococcus aureus,Bacil- lus pyocyaneus,Escherichia coli,Streptococcus A,B and C.It was shown that SWDGY possessed anti-inflammatory,analgesic and antiseptic effects in vitro.In mice LD_(50) of SWDGY by oral administration was more than 840g/kg.Affer cral adminstration in a daily dose of 189.Sg/kg continuously for one month in rats, no toxic reactions appeared,This dosage was 118.6 times as much as the clinical one.
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Objective: To observe the main pharmacodynamic effects of Yinaoning (YNN) on acute blood stasis rats and cerebral ischemia rats. Methods: Rats were prevented by the oral administration of YNN (0.4375～ 1.75g/kg once daily for 7 days. The acute blood stasis model and cerebral ischemaed model were used. Results: YNN could decrease the blood viscosity and plasma viscosity, shorten the length of in vitro thrombus, abate the wet and dry weights of thrombus in the acute blood stasis model group. It decreased the brain index significantly in the cerebral ischemia model group. The high dose of YNN could decrease the level of Evans blue obviously and reduce the degeneration of cranial nerve cells. These effects were similar to those of YNN Tablets and were dose dependent. Conclusion: YNN is effective for acute blood stasis rats and cerebral ischemaed rats.
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Ketoconazole(KET) is a new imi-dazole derivative with broad antimycotic spectrum. In order to verify the clinical toxic and side effect and its properties in animals, we made a long-term toxicity test for 30 days. Dosages of 70, 35 and 17. 5 mg?kg-1?d-1(e-quivalent to 21, 10. 5 and 5. 2 times of the clinical dosage) were given ig to dogs. The salivation , vomiting, anorexia, decrease in heart rate and loss of weight occurred in the large dosage group. Half of the dogs died from toxicosis within ig 15 days. Laboratory examination showed that the activities of ALT, LDH and ALP, the content of T-BIL, BUN in serum in-creased in this group. Pathological examination revealed that there were some pathological changes in the liver, kidneys, adrenal glands and sex gland in the group. There were no significant changes in other dosage groups compared with the normal control group. After withdrawal of KET, all toxic symptoms disappeared and the abnormal indexes were restored. The results indicated that toxic target organs of KET were liver, kidney, adrenal gland and sex glands. The safe dosage for dogs was about 17. 5 mg?kg-1?d-1.
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The effects of amino acid electuary (Ganan Elemental Granules) on experimental acute hepatic failure induced by D-galactosamine in rats were studied. The results showed that the electuary could significantly prevent the decrease in body weight and food intake, the prolongation in time of blood coagulation time and increase in the levels of serum glutamic-pyruvic transaminase activity, elevate contents of total serum protein and serum albumin, normalize the serum ratio of BCAA to AAA and disordered amino acid pattern, increase survival of animals and improve encephalopathy in rats with acute hepatic failure. These results suggest that the amino acid electuary has a better protective effects on acute hepatic failure.
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The effects of amino acid electuary on experimental liver fibrosis in rats with chronic liver injury induced by CCI4 were studied. The results showed that the electuary could prevent the decrease in body weight and food intake, reduce the levels of serum glutamic-pyruvic transaminase activities, elevate contents of total serum protein and serum albumin, normalize the serum ratio of BCAA to AAA and disordered amino acid pattern and suppress degeneration, necrosis and fibrosis of liver tissues in rats with chromc liver injury. These results indicate that the amino acid electuary has beneficial effects in prevention and treatment of liver fibrosis.
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In this paper the subacute toxicity of the new photosensitizer FSD-007 in dogs is reported. The manifestations of its subacute toxicity such as salivation, nausea, vomi-tus and other early syndromes were similar to those of porphyrinemia. The laboratory findings showed that the red cell system was depressed markedly, and hepatic and renal functions were impaired to some extent. These lesions were reversible and coincident with what was observed in its acute toxicity. The experimental results have further provided the evidence that these may be used clinically fer guard against its toxic effects.The results of phase I of clinical pharmacological study of FSD-007 have shown that there were no toxic effects observed after 2.5-5.0mg/kg iv on condition that the patient were kept away from direct sunlight for a month. And its subacute toxieity test has demonstrated that all its toxic changes arc dose-related,reversible and predictable. This preparation, therefore, may be safely tested in phase II with same dosage, but no duplicate administration is permitted within two weeks.
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The factors which had an influence on the phototoxic effect of the photocarcino-rin were studied in mice.The phototoxic reaction was correlated with the doses of the drug and irradiation time.The phototoxic reaction did not develop in mice by topical administration of the drug in ears or when there was an interval (72h) between intravenous injection and irradiation.