Ensayo de inmunogenicidad y toxicidad aguda del candidato vacunal contra el cólera vax-COLER® / Immunogenicity and acute toxicity assay of the vaccine candidate against cholera vax-COLER®

Para el control y prevención del cólera humano se han llevado a cabo diferentes estrategias, entre las cuales, la vacunación es una de las medidas más eficaces. La evaluación preclínica de candidatos vacunales requiere de la demostración de la seguridad de los mismos, para lo cual los estudios toxicológicos son determinantes, al ser obligatorios y altamente regulados. Este estudio tuvo como objetivo demostrar la relevancia de las ratas Sprague Dawley como biomodelo a través de su respuesta inmunológica al candidato vacunal contra el cólera, vax-COLER®, utilizando la técnica de determinación de anticuerpos vibriocidas. Además, evaluar los efectos toxicológicos locales y sistémicos por la administración de una dosis de vax-COLER® a través de la evaluación de síntomas, del consumo de agua y alimentos, el peso corporal y estudios anatomopatológicos. La vacuna vax-COLER® resultó inmunogénica y no evidenció síntomas ni muertes, no hubo cambios en el peso corporal y los consumos de agua y alimentos se comportaron de forma similar entre todos los grupos. Los estudios anatomopatológicos solo mostraron cambios a nivel histológico en los ganglios linfáticos mesentéricos y placas de Peyer de los animales vacunados, con presencia de hiperplasia de los folículos secundarios subcapsulares, hallazgo que difirió significativamente con el resto de los grupos. Se concluye que la vacuna vax-COLER® es inmunogénica en ratas Sprague Dawley, demostrando la relevancia del biomodelo para la evaluación de la seguridad preclínica y que la aplicación de una dosis no produjo efectos tóxicos agudos generales ni locales(AU)

Different strategies have been carried out for the control and prevention of human cholera. Vaccination is one of the most effective strategies. Preclinical evaluation of vaccines needs to prove their safety; whereby toxicological studies are decisive. They are mandatory and highly regulated. This study was aimed to demonstrate the relevance of Sprague Dawley rats as a biomodel, through the immunological response to vax-COLER® cholera vaccine, using the technique of determination of vibriocidal antibodies. In addition, local and systemic toxicological effects were evaluated after administration of a dose of vax-COLER®; through the evaluation of symptoms, water and food consumption, body weight and anatomopathological studies. The vax-COLER® vaccine was immunogenic and showed no symptoms or deaths. No changes in body weight were detected, and food and water consumption were similar among all groups. The anatomopathological studies showed histological changes in the mesenteric lymph nodes and Peyer's patches of the vaccinated animals, with hyperplasia of the subcapsular secondary follicles, finding that differed significantly from the rest of the groups. It is concluded that vax-COLER® vaccine is immunogenic in Sprague-Dawley rats, demonstrating the relevance of the biomodel for the evaluation of preclinical safety, as well as that the application of a single dose did not produce acute general or local toxic effects(AU)

Role of C-Jun N-terminal kinase signal transduction pathway in spinal neurotoxicity induced by lidocaine in rats / 中华麻醉学杂志

Objective To evaluate the role of C-Jun N-terminal kinase (JNK) signal transduction pathway in spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-260 g,were randomly divided into 6 groups (n =12 each):control group (group Ⅰ),sham operation group (group Ⅱ),JNK inhibitor group (group Ⅲ),dimethyl sulfoxide (DMSO) group (group Ⅳ),lidocaine group (group Ⅴ),and JNK inhibitor and lidocaine group (group Ⅵ).Group Ⅰ received no treatment.Intrathecal catheter was placed in the subarachnoid space in group Ⅱ.SP600125 25 μg and DMSO 20 μl were injected intrathecally in Ⅲ and Ⅳ groups,respectively.In group Ⅴ,10％ lidocaine 20 μl was intrathecally injected.SP600125 25 μg was injected intrathecally and 30 min later 10％ lidocaine 20 μl was injected intrathecally in group Ⅵ.Paw withdrawal threshold to yon Frey filament stimulation (PWT) and paw withdrawal latency to nociceptive thermal stimulation (PWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration,4 rats were randomly chosen from each group and sacrificed.Their lumbar enlargements were removed for determination of phosphorylated JNK (p-JNK) expression (using Western blot) and neuronal apoptosis (by TUNEL).The apoptotic index was calculated.Results Compared with group Ⅰ,no significant difference was found in MWT and TWL in Ⅱ,Ⅲ groups and expression of p-JNK in Ⅱ and Ⅳ groups (P ＞ 0.05),MWT at T2-4,6-8 and TWL at T2-4,7 in group Ⅴ and MWT at T2-6 and TWL at T2-5 in group Ⅵ were significantly increased,the expression of p-JNK was down-regulated and the apoptotic index was decreased in group Ⅲ (P ＜ 0.05),and the expression of p-JNK was up-regulated and the apoptotic index was increased in Ⅴ and Ⅵ groups (P ＜ 0.05).Compared with group Ⅴ,MWT and TWL were significantly decreased,the expression of pJNK was down-regulated and the apoptotic index was decreased in group Ⅵ (P ＜ 0.05).Conclusion Activation of JNK signal transduction pathway is involved in spinal neurotoxicity induced by lidocaine in rats possibly through promoting neuronal apoptosis in the spinal cord.

Acute toxicity of intravenous isoflurane in Beagles / 中华麻醉学杂志

Objective To investigate the acute toxicity of intravenous isoflurane in Beagles.Methods Six healthy adult Beagles of both sexes aged 6-8 months weighing 6-8 kg were used in this study.Isoflurane injectio (120 mg/ml) in 30% hpid emulsion was injected intravenously. Femoral artery was cannulated for direct BP monitoring.ECG was continuously monitored.The maximal tolerance dose (MTD) and approximate lethal dose (ALD) were determined by up-and-down technique. The initial dose was 3.0 ml/kg. The dose was decreased/increased by 0.3 ml/kg if the previous animal died/survived.The survived dogs were observed for 2 weeks.Autopsy and histopathological examination were performed on all dead Beagles.Results The ALD and MTD of intravenous isoflurane were 252 and 216 mg/kg. Autopsy and histopathological examination did not show any abnormality.Conclusion Cardiopulmonary depression is the main manifestation of the acute toxicity of intravenous isoflurane in Beagles.

Acute toxicologic study on Wuweizi Ningshen oral liquid / 中国基层医药

Objective To abserve the acute toxicity in mice administered with Wuweizi Ningshen oral liquid.Methods The maximum administration dosage(MAD)of Wuweizi Ningshen oral liquid were determined by administration intragastricly in mice.Wuweizi Ningshen oral liquid was administered for 2 weeks,and the growth condition,body weight growth and index of main viscera were measured.Results The index of growth condition,body weight growth and index of main viscera were in normal ranges.Conclusion It could be concluded that Wuweizi Ningshen oral liquid is safe to be administered in the dose prescribed.

Acute toxicity of meso-2,3-dimercaptosuccinic acid on mice / 中国基层医药

Objective To explore acute toxicity of succimer on mice.Methods Twenty Kunming mice(10 males and 10 females) weighting approximately (21.2?2.3)g were acclimatized for 3 days prior to dosing,then were divided into control group and experiment group with 10 mice in each group according to body weight.Fasted for 12 hours,the mice in experiment group received intragastric administration of 160mg DMSA in deionized water in 24 hours,and the control group received the same volume of deionized water,and then they were observed for 7 days.Blood was collected into heparinized-tubes by removal of eyeball.All mice were sacrificed and brain,heart,liver and kidney were removed and washed with normal saline.The activity or amount of BUN,Scr,AST,ALT,SOD, GSH-PX and MDA were analyzed.Results (1)Given 160rag DMSA in 24 hours,gastrointestinal symptoms were main side effects.During the observation,experiment group lost weight due to the decrease of food-intake ,and some mice had slight hydroabdomen.(2)High dose of DMSA caused a significant inhibition of GSH-PX(P0.05).The hepatic cell was damaged accord- ing to the significant raise of MDA in liver(P0.05),which was related to acute toxicity on liver.Conclusion Succimer could inhibit the antioxidarrt systems and could do damage to liver and kidney.

Acute Toxicity Test of Baicalein Capsule in Mice / 医学研究杂志

Objective To observe the acute toxic reaction and death of mice one day after intragastric administration of Baicalein capsule so as to appraise its safety.Methods The ICR mice were intragastrically administered with Baicalein powder at maximum concentration. There was no death of mice found and no LD50 detected. Hence the maximum dosage was measured. Results The maximum dosage of Baicalein powder is 15g/kg. Conclusions The Baicalein capsule is relatively safe.

Toxic Reactions of Memantine in Acute Toxicologic Experiment in Neonatal Rats / 实用儿科临床杂志

Objective To explore the acute toxic reactions of memantine in neonatal rats. Methods Based on Completely Lethal dose(LD_(100)) and median lethal dose (LD_(50))of memantine in SD neonatal rats acquired in a preliminary test of death dose, 60 neonatal rats were randomly divided into normal group which were given water injection intraperitoneally and 5 study groups which were given different doses of memantine intraperitoneally.LD_(50) was calculated with Bliss method and the toxic reactions of memantine were observed in all neonatal rats of 6 groups after administration of memantine. Results LD_(50) of memantine in SD neonatal rats was((74.386?2.811)) mg/kg with 95% confidence at the range of 59.334-93.257 mg/kg.Side effects occurred at 1-4 minutes after administration. Excitatory jitteriness,ataxia,decreased respiratory rate and passivity were usually observed in groups with a lower dosage (52.0 mg/kg,61.2 mg/kg,72.0 mg/kg);some of them also manifested side lying, cyanosis and respiratory failure.While neonatal rats with a higher dosage (85 mg/kg,100 mg/kg)mainly manifested visible symptoms of inhibition, respiratory failure,side (lying) and cyanosis.However,no jitteriness and ataxia were observed in them.The neonatal rats usually died around 1 hour after memantine administration;survival rats usually returned to normal 4-5 hours after administration.Conclusion There is a positive correlation between toxic reactions and the mortality with memantine dosage in neonatal rats.

Pathological Changes of Memantine in Neonatal Rats in Acute Toxicologic Experiment / 实用儿科临床杂志

Objective To investigate the pathomorphology effects of memantine on organs in neonatal rats.Methods Sixty-eight neonatal rats were randomly divided into 7 groups:5 groups by different doses memantine intraperitoneally and the controls by water intraperitoneally.The pathomorphology changes of organs were observed in all dead neonatal rats promptly after administration of memantine and in all survived rats after 7 days recover.Results 1.The ratio of organ weight and body weight in dead neonatal rats were higher than those of controls.2.The result of pathomorphology indicated that neurodegeneration and necrosis in the brain,the liver congestion and cell degeneration.The other organs had not distinct changes.3.The pathologic changes and mortality rate of neonatal rats were positively correlated with the dosage of memantine.Conclusion Memantine will affect liver and brain of neonatal rats.

Toxicology of Sanqi Shuishu Capsule / 中成药

AIM: To study toxicology of Sanqi Shuishu Capsule (SQSS) (Panax Notoginseng, Semen Ziziphi Spinosae; Fructus Schisandrae, etc). in order to establish a theoretical basic for clinical use. METHODS: With the aid of the acute toxicity tests, the inheritance toxicity tests, feeding the rat on trial research for 30 d, we observed the toxicology of SQ SS Capsule. RESULTS: SQ SS Capsule had not action of mutation, micronucleolus proliferation of rat's marrow polychrouiatic erythrocytes increase, and rat's sperm malformation. CONCLUSION: Poisonous effect has not been observed in SQ SS Capsule.