RESUMEN
Use of the elevated plus-maze experiment and activity and traction tests in mice have revealed that seven daily treatments with 0.2 mg kg(-1) and higher doses of honokiol, a neolignane derivative extracted from Magnolia bark, had an anxiolytic effect without change in motor activity or muscle tone. Diazepam, 1 mg kg(-1), had the same anxiolytic potential as 0.2 mg kg(-1) honokiol but induced muscle relaxation. The aim of this study was to determine whether honokiol had diazepam-like side-effects. Mice treated with 1-10 mg kg(-1) diazepam, but not those treated with 0.1-2 mg kg(-1) honokiol, for 12 days showed withdrawal symptoms characterized by hyperactivity and running-fit when they were challenge-administered intraperitoneal flumazenil (10 mg kg(-1)) 24 h after the last treatment with diazepam. Oral diazepam (0.5-2 mg kg(-1), 10 min before) dose-dependently prolonged hexobarbital (100 mg kg(-1), i.p.)-induced sleeping, disrupted learning and memory, and inhibited (+)-bicuculline (40 mg kg(-1), i.p.)-induced death. Honokiol (0.2-20 mg kg(-1), p.o., 3 h before) had no such effects. The prolongation by diazepam (1 mg kg(-1)) of hexobarbital-induced sleeping was not modified by honokiol (0.2-20 mg kg(-1)). These results suggest that honokiol is less likely than diazepam to induce physical dependence, central depression and amnesia at doses eliciting the anxiolytic effect. It is also considered that honokiol might have no therapeutic effect in the treatment of convulsion.
Asunto(s)
Ansiolíticos/toxicidad , Conducta Animal/efectos de los fármacos , Compuestos de Bifenilo/toxicidad , Diazepam/toxicidad , Lignanos , Animales , Bicuculina/toxicidad , Hexobarbital/farmacología , Aprendizaje/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Sueño/efectos de los fármacos , Trastornos Relacionados con SustanciasRESUMEN
Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test. In the plus-maze test a single oral dose of 20 mg kg(-1) honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg(-1). The maximum effect was observed for doses of 0.5 mg kg(-1). Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5-2 mg kg(-1), caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg(-1), and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg(-1) honokiol and after a single treatment with 1 mg kg(-1) diazepam were almost equivalent. The effect of honokiol (0.2 mg kg(-1), treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg(-1)) and (+)-bicuculline (0.1 mg kg(-1)) and by intraperitoneal CCK-4 (50 microg kg(-1)) and caffeine (30 mg kg(-1)). The anxiolytic effect of diazepam (1 mg kg(-1)) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4. These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or disinhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.
Asunto(s)
Ansiolíticos/farmacología , Compuestos de Bifenilo/farmacología , Depresores del Sistema Nervioso Central/farmacología , Lignanos , Aprendizaje por Laberinto/efectos de los fármacos , Administración Oral , Animales , Ansiolíticos/administración & dosificación , Bicuculina/administración & dosificación , Bicuculina/farmacología , Compuestos de Bifenilo/administración & dosificación , Cafeína/administración & dosificación , Cafeína/farmacología , Depresores del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/farmacología , Diazepam/administración & dosificación , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Flumazenil/administración & dosificación , Flumazenil/farmacología , Antagonistas del GABA/administración & dosificación , Antagonistas del GABA/farmacología , Moduladores del GABA/administración & dosificación , Moduladores del GABA/farmacología , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos BALB C , Actividad Motora/efectos de los fármacos , Tetragastrina/administración & dosificación , Tetragastrina/farmacología , Equivalencia TerapéuticaRESUMEN
The acetylcholine contents of mouse brain regions were measured in order to investigate the response of cholinergic neurons to electroshock. In this study, mice were subjected to electroshock and then sacrificed by microwave irradiation at time intervals of from 0.4 to 6.9 a after electroshock. In all of the brain regions studied, the acetylcholine concentration appeared to oscillate with a mean period of approximately 2.5 a following electroshock. The rate of recovery of acetylcholine after electroshock was calculated for each brain region from the oscillatory equation obtained by nonlinear regression analysis of the experimental data. The rates of synthesis of acetylcholine derived from these in vivo measurements were substantially higher than have been indicated by other methods.
Asunto(s)
Acetilcolina/metabolismo , Encéfalo/metabolismo , Neuronas/metabolismo , Acetilcolina/biosíntesis , Animales , Encéfalo/citología , Electrochoque , Hidrólisis , Masculino , Ratones , Ratones Endogámicos ICR , Microondas , Análisis de RegresiónRESUMEN
Among the many rapidly metabolized compounds in the brain, acetylcholine is one of the most challenging to sample effectively due to its rapid synthesis, degradation and sequestration. To ascertain problems that invalidate sampling procedures two methods of tissue fixation, microwave heat inactivation and freeze fixation, were used for obtaining mice and rat brain samples, respectively. The data show that acetylcholine levels obtained by microwave fixation were much higher than those obtained by freeze fixation. Choline levels were not affected by the fixation method used. Microwave fixation results in more accurate assessment of acetylcholine levels than the freeze fixation method, even though the tissue fixation time was less than 1 s in both methods, because tissue integrity is maintained in the microwave fixation, but not during freeze fixation.
Asunto(s)
Acetilcolina/metabolismo , Encéfalo/metabolismo , Colina/metabolismo , Animales , Encéfalo/efectos de la radiación , Química Encefálica , Cromatografía Líquida de Alta Presión , Congelación , Masculino , Ratones , Ratones Endogámicos BALB C , Microondas , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Fijación del TejidoRESUMEN
A new antiinflammatory agent identified as 8-[C-beta-D-[2-O-(E)-cinnamoyl]glucopyranosyl]-2- [(R)-2-hydroxypropyl]-7-methoxy-5-methylchromone (1) has been isolated from Aloe barbadensis Miller. At a dose of 200 microg/mouse ear, 1 exhibited topical antiinflammatory activity equivalent to 200 microg/ear of hydrocortisone. There was no reduction in thymus weight caused by treatment with 1 for any of the doses tested, while 200 microg/ear of hydrocortisone resulted in a 50% decrease in thymus weight.
Asunto(s)
Aloe/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Cromonas/aislamiento & purificación , Plantas Medicinales , Animales , Antiinflamatorios no Esteroideos/farmacología , Cromatografía Líquida de Alta Presión , Cromonas/farmacología , Aceite de Crotón , Oído Externo/patología , Cromatografía de Gases y Espectrometría de Masas , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/prevención & control , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Espectrofotometría UltravioletaRESUMEN
Food restriction (FR), which extends life span, is associated with an enhanced diurnal elevation of glucocorticoids. This increase in glucocorticoids may contribute to longevity by chronically enhancing the same protective mechanisms mobilized during acute stress. The objective of this study was to determine if attenuation of inflammation, a presumably protective effect of glucocorticoids, occurs in FR mice. Two-month-old male BALB/c mice were either fed ad lib (AL) or FR (60% AL calories) for 2 months. After one month, the diurnal elevation of plasma corticosterone was threefold higher in FR mice. Two weeks after corticosterone sampling, a hind foot pad of each mouse was injected with 20 microliters of 4% carrageenan. Maximum observed edema did not differ between FR and AL groups, but edema was reduced at onset and fell earlier in FR mice. Results indicate that at least one inflammatory reaction is attenuated by FR and are consistent with the hypothesis that FR enhances a potentially protective glucocorticoid activity.
Asunto(s)
Corteza Suprarrenal/fisiología , Edema/fisiopatología , Ingestión de Energía/fisiología , Alimentos , Enfermedades del Pie/fisiopatología , Longevidad/fisiología , Corteza Suprarrenal/anatomía & histología , Animales , Peso Corporal , Carragenina/efectos adversos , Ritmo Circadiano/fisiología , Corticosterona/sangre , Corticosterona/fisiología , Edema/patología , Enfermedades del Pie/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos , Timo/anatomía & histologíaRESUMEN
Accurate knowledge of the concentration in the central nervous system of neurochemicals undergoing rapid enzymatic destruction or synthesis is sparse because of the difficulty in stopping the rapid reactions while causing only minimal adverse changes in the neurochemistry and structure. Microwave heating can be effectively used to rapidly stop enzyme activity in the central nervous system with minimal adverse changes. This rapid inactivation of the enzymes increases the validity of the sample that is taken for analysis of the concentration of the enzyme's substrate.
Asunto(s)
Microondas , Fijación del Tejido/métodos , Animales , Química EncefálicaRESUMEN
The croton oil ear test is widely used to identify prospective topical antiinflammatory drugs. Ear inflammation is produced by applying a 2% solution of croton oil on the ears of mice or rats. The effectiveness of the drug that is dissolved in the croton oil solution can be gauged by comparing the croton oil treated ears with the croton oil plus drug treated ears. The effect is measured following sacrifice of the animal by weighing either the excised ear (Tonelli et al., 1965; Glenn et al., 1978; Swingle et al., 1981; Soliman et al., 1983; Mantione and Rodriguez 1990) or a plug taken from the ear (Tubaro et al., 1985; Davis et al., 1989a; Davis et al., 1989b). Use of this technique for the generation of a time-course evaluation of antiinflammatory activity requires a large amount of the chemical to be tested and the sacrifice of many animals. In other assays, ear thickness has been measured by caliper (Carlson et al., 1985; Maloff et al., 1989) or by dial micrometer (Griswold et al., 1987), which allow multiple measurements to be made, but the pressure on the ear was not reported. In a recent review of pharmacological methods, Chang and Lewis (1989) caution that using calipers to measure ear thickness is subject to operator error and bias. Furthermore, they emphasize care must be taken to not leave the calipers in contact with the ear too long, as it is possible to squeeze substantial amounts of edema fluid out of the ear tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Oído/patología , Inflamación/patología , Animales , Antiinflamatorios , Aceite de Crotón , Relación Dosis-Respuesta a Droga , Hidrocortisona/farmacología , Inflamación/inducido químicamente , Ratones , RatasRESUMEN
The identification of sacrifice methods that produce reliable measures of baseline central nervous system neurotransmitter concentrations poses a challenge to analytical neurochemical investigation. In the present study, microwave irradiation (MWVI) was compared with in situ freezing, cervical dislocation, and simple decapitation, in an effort to examine their effects on whole mouse brain concentrations of 3-methoxytyramine (3MT) and normetanephrine (NMN), the O-methylated catecholamine metabolites believed to be sensitive indicators of release of CNS dopamine and norepinephrine, respectively. Both high-energy (6 kW, 0.3 s) and low-energy (2.5 kW, 1.5 s) MWVI produced the lowest mouse brain concentrations of 3MT and NMN when compared with other methods of sacrifice within experiments. In situ freezing resulted in values of 3MT and NMN that were slightly, yet significantly, higher than MWVI within experiments. The concentrations of 3MT and NMN obtained following either cervicle dislocation or simple decapitation were up to 9-fold greater than those produced by either of the two previous methods.
RESUMEN
Male Sprague-Dawley rats were trained on a discriminated avoidance-escape task. They were administered subchronically saline, 12.7 micrograms/kg (0.125 LD50) soman, or 25.5 micrograms/kg (0.25 LD50) soman. Injections were given 5 days per week for 4 weeks. Injections were given subcutaneously immediately following the avoidance behavior test session. Soman produced a reduction in avoidance behavior efficiency in a dose dependent manner. When soman was discontinued, the rats recovered their pre-soman control baselines. Untrained rats given soman according to the same soman regimen were used to measure acetylcholine in brain and cholinesterase activities in brain, blood, and diaphragm. After 18 soman injections at 12.7 and 25.5 micrograms/kg acetylcholine was reduced significantly only in the amygdala. Blood cholinesterase was inhibited as much as 57% after 12.7 micrograms/kg soman and 74% after 25.5 micrograms/kg. Plasma cholinesterase was inhibited to 24% by the 12.7 micrograms/kg dose of soman and to 38% by the 25.5 micrograms/kg dose. Plasma cholinesterase recovered to control levels 11 days after cessation of soman, and whole blood cholinesterase recovered 25 days after cessation of the higher soman dose. Cholinesterase was inhibited significantly in the hippocampus and amygdala in a dose dependent manner. The cholinesterase activities appear to parallel the soman induced decrement in avoidance behavior and the subsequent recovery to control levels following withdrawal of soman.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Inhibidores de la Colinesterasa , Soman/toxicidad , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Colinesterasas/sangre , Relación Dosis-Respuesta a Droga , Reacción de Fuga/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Soman/administración & dosificaciónRESUMEN
Acetylcholine (ACh) was measured from birth to the 78th day in 11 mouse brain regions. Three patterns of development emerged: ACh increased rapidly, overshot and returned to the adult level in midbrain-medulla-pons and cerebellum, ACh increased linearly to adult level in neostriatum and olfactory bulb and ACh increased linearly to a plateau and then increased to the adult level in the remaining regions.
Asunto(s)
Acetilcolina/análisis , Química Encefálica , Acetilcolinesterasa/análisis , Envejecimiento/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Colina O-Acetiltransferasa/análisis , Ratones , Ratones Endogámicos , Proteínas del Tejido Nervioso/análisisRESUMEN
The convulsant pentylenetetrazole was administered to the lower primate, the tree shrew. Shortly after the onset of seizures, the animals were killed using a microwave device at 25 Kw and 915 MHz. The energy metabolites glycogen, glucose, ATP, and phosphocreatine were measured in five layers of the cerebral cortex and three layers of the cerebellum. Results showed that, as compared with controls, seizing animals had decreased energy metabolites selective to certain layers. Glucose was decreased in all cortical layers, but only in the granular layer of the cerebellum. Phosphocreatine was decreased in the outer small pyramidal layer and the polymorphous layer of the cortex but was unchanged in the cerebellum. ATP was decreased only in the outer small polymorphous layer of the cortex. These changes are consistent with the concept that selective changes may occur during seizures and that these changes are localized to layers that contain pyramidal cells. Examination of whole cortex may mask more subtle regional changes.
Asunto(s)
Encéfalo/metabolismo , Metabolismo Energético/efectos de los fármacos , Pentilenotetrazol/farmacología , Convulsiones/metabolismo , Tupaia/metabolismo , Tupaiidae/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Cerebelo/metabolismo , Corteza Cerebral/metabolismo , Femenino , Glucosa/metabolismo , Glucógeno/metabolismo , Fosfocreatina/metabolismo , Convulsiones/inducido químicamenteRESUMEN
We demonstrate that microwave (MW) energy can be used in conjunction with chemical cross-linking agents to fix tissue blocks rapidly for electron microscopy in as brief a time as 26 msec. The optimal ultrafast MW fixation methodology involved immersing tissue blocks up to 2 mm3 in dilute aldehyde fixative and immediately irradiating the specimens in a 7.3 kW MW oven for 26-90 msec, reaching a fixation temperature range of 32-42 degrees C. Ultrastructural preservation of samples irradiated by MW energy was comparable to that of the control samples immersed in aldehyde fixative for 2 hr at 25 degrees C. Potential applications for this new fixation technology include investigation of rapid intracellular processes (e.g., vesicular transport) and preservation of proteins that are difficult to demonstrate with routine fixation methods (e.g., antigens and enzymes).
Asunto(s)
Hígado/ultraestructura , Microscopía Electrónica/métodos , Microondas , Miocardio/ultraestructura , Animales , Fijadores , Ratones , Ratones Endogámicos ICR , Factores de TiempoRESUMEN
Ammonia levels are elevated in many patients with hepatic encephalopathy. This observation, coupled with animal studies showing an encephalogenic role for ammonia, has led to the concept that ammonia is an important toxin in the production of neurologic symptoms. Studies in rodents have shown that ammonia alters cerebral energy metabolism in the reticular formation, an area important in the modulation of consciousness. Our study was undertaken to extend these observations to the lower primate Tupaia glis, the tree shrew. The energy metabolites glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine were measured in the reticular formation by microanalytic techniques and enzymatic cycling. Acetylcholine was measured in brain regions by gas chromatography. Acetylcholine levels were increased significantly only in the medulla-pons and diencephalon in the coma stage. The energy metabolites glucose, glycogen, and phosphocreatine were decreased in reticular formation cells during the coma, whereas lactate was increased. During the precoma, glycogen and phosphocreatine were decreased. It appears, therefore, that the tree shrew has a metabolic response to ammonia similar to that of mice. A lowering of energy metabolism in the area of brain-regulating consciousness may act to place the animal in a coma. This coma in turn acts to decrease overall metabolic demand, which allows the animal an opportunity to conserve its threatened energy reserves.
Asunto(s)
Acetilcolina/metabolismo , Amoníaco/envenenamiento , Encéfalo/efectos de los fármacos , Coma/metabolismo , Metabolismo Energético/efectos de los fármacos , Acetatos/envenenamiento , Animales , Encéfalo/metabolismo , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/metabolismo , Coma/inducido químicamente , Femenino , Encefalopatía Hepática/metabolismo , TupaiaRESUMEN
A thermoviewer, a new model of JTG-500 (JEOL, Japan) was utilized for finding the effect of microwave heat energy absorption and its conductivity in the brains of rats and mice following microwave irradiation (MWR). The frozen head was cut in either the sagittal, frontal or horizontal plane. After the frozen brain returned to room temperature (27-28 degrees C), the parts were put together with scotch tape and place in the exposure chamber. The rat's brain was irradiated at 6 kW for 0.6 sec and the mouse's brain was irradiated at 6 kW for 0.12 sec. Within 2 min. after irradiation, one side of each head was removed from the body and set in front of the camera unit. Each frame of a thermal image with its temperature information was stored in a data memory and the image of the brain surface was displayed at a flickerfree TV rate under the most optimum display condition. The temperature resolution of the device was 0.05 degrees C. In the individual rat planes, the highest energy was efficiently centralized in the middle of each individual plane and was distributed to the periphery showing phased decreases in temperature. The temperature differences recorded in the rat's sagittal, frontal and horizontal sections were; 4.6 degrees C, 5.0 degrees C and 3.4 degrees C, respectively. Temperature differences in rat brains irradiated by MWR were known to be below 5.0 degrees C under these experimental conditions. In the mouse planes, the highest level of microwave energy was also centralized in the middle of each individual section.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Temperatura Corporal , Encéfalo/fisiología , Microondas , Termografía , Animales , Encéfalo/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos ICR , Ratas , Ratas Endogámicas , Termografía/instrumentaciónRESUMEN
A method is described in which brain tissue from microwave heat inactivated mouse brain is prepared for microregional energy metabolite analysis. This method permits the sectioning of the tissue into sections 40 microns thick in which layers can be visualized and dissected. Results show no movement or leaching of metabolites from one microregion to another. This method therefore, permits the combined use of the two powerful neurochemical techniques of microwave irradiation for sacrifice and microregional analysis for energy metabolite determination.
Asunto(s)
Adenosina Trifosfato/análisis , Química Encefálica/efectos de la radiación , Microondas , Neuroquímica/métodos , Fosfocreatina/análisis , Animales , Femenino , RatonesRESUMEN
A new model of a microwave device was developed with a power of 10 kW at 2450 MHz. In order to accomplish even distribution of heating with minimum trauma and with a maximum certainty about enzyme inactivation, a modified magnetic field distribution was utilized rather than the conventional electric field. An integrated tuning system was used to increase efficiency and distribution of microwave energy absorption. This increased the ability of the instrument to properly inactivate the enzymes in the brain of both mice and large rats. In general, the time of irradiation for the rat was 600 to 900 msec and for the mice, 100 to 330 msec. The animal chambers used were designed so as not to impair breathing or too severely restrict movement. The effects of these improvements on microwave irradiation were confirmed by 1) observation of brain appearance, 2) effects on succinic dehydrogenase and cholinesterase activity, 3) measurement of regional temperatures in the animal's brain, 4) thermograms of the brain, 5) electron microscopic examination of brain tissue and 6) measurement of endogenous acetylcholine and catecholamines.
Asunto(s)
Acetilcolinesterasa/metabolismo , Encéfalo/enzimología , Microondas , Succinato Deshidrogenasa/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Acetilcolina/metabolismo , Animales , Temperatura Corporal , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Catecolaminas/metabolismo , Calor , Masculino , Ratones , Ratas , Ratas EndogámicasRESUMEN
To update the status of chymopapain in the treatment of herniated intervertebral discs, a review of the current literature and data from an unpublished Texas study are presented. Studies in animals and humans have consistently demonstrated that chymopapain can dissolve the nucleus pulposus. Twenty-eight uncontrolled and unblinded clinical trials involving 2845 patients showed a positive response rate of 75%. Side effects occurred in 2.4% of chymopapain-treated patients. Anaphylaxis, the most serious adverse reaction associated with chemonucleolysis, was noted in less than 1% of patients. No deaths were reported. The first double-blind, placebo-controlled study of chymopapain in the United States demonstrated no significant efficacy, but both the design and execution of the study have been criticized. Two recent double-blind, placebo-controlled studies showed success rates of 73% and 80% for chymopapain, significantly higher than for placebo treatment. Postinjection back pain and muscle spasm were the most common side effects related to chymopapain administration in one of the trials. In the uncontrolled Texas study the success rate in 408 patients treated by chymopapain was 93%. Chemonucleolysis has achieved a success rate comparable with that of surgery in the treatment of symptomatic herniated discs. Appropriate use of chymopapain can result in substantial savings in time and hospital costs.
Asunto(s)
Quimopapaína/uso terapéutico , Endopeptidasas/uso terapéutico , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Anafilaxia/etiología , Animales , Quimopapaína/administración & dosificación , Quimopapaína/efectos adversos , Ensayos Clínicos como Asunto , Método Doble Ciego , Estudios de Seguimiento , Hemorragia/inducido químicamente , HumanosRESUMEN
The median lethal dose (LD50) of chymopapain B in mice was 82 mg/kg (22,000 units/kg) with 95% confidence limits of 75-90 mg/kg (20, 122-24, 146 units/kg) and in rats 92 (24,683 units/kg) with 95% confidence limits of 83-102 mg/kg (22,268-27, 366 units/kg). The mechanism of toxicity was hemorrhage due to destruction of the cement substance of the blood vessels. Intervertebral disc injection of chymopapain B in the rabbit at a dose level of 186 micrograms (50 units) caused chemonucleolysis in 67% of the rabbits as evidenced by partial dissolution of the nucleus pulposus. Chemonucleolysis was also noted at higher doses. No adverse affects were noted with a 20 fold increase to 3.7 mg (1000 units). A dose of 18.6 mg (5000 units)/disc caused paralysis of the hindlegs. A dose as high as 26.6 mg (7143 units) /disc caused nearly complete dissolution of the nucleus pulposus and can cause disruption of the annulus fibrosus and death. Guinea pigs receiving a sensitizing dose of 0.003 mg/kg (0.8 units/kg) chymopapain B intraperitoneally six times over two weeks were challenged with an intravenous dose of 0.03 mg (8 units)/kg. All animals exhibited marked anaphylactic signs with a resulting 50% fatality rate.
Asunto(s)
Quimopapaína/toxicidad , Endopeptidasas/toxicidad , Anafilaxia/inducido químicamente , Animales , Quimopapaína/administración & dosificación , Femenino , Cobayas , Inyecciones , Inyecciones Intravenosas , Disco Intervertebral , Dosificación Letal Mediana , Masculino , Ratones , Conejos , Ratas , Ratas EndogámicasRESUMEN
Mice were exposed to a single 15-ms or 25-ms pulse of 2,450-MHz microwaves which increased brain temperature by 2 degrees C or 4 degrees C, respectively. Immediately after exposure, the mice became hypokinetic but began recovering within 5 minutes. The 25-ms pulse (18.7 j deposited in the brain) caused a significant decrease in acetylcholine content of the whole brain, probably owing to increased permeability of the membrane.