ABSTRACT
The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) may have therapeutic potential for preventing and treating cocaine addiction. Previously, we found that transplantation of a GDNF-expressing astrocyte cell line into the striatum and nucleus accumbens attenuates cocaine-seeking behavior in Sprague-Dawley rats. However, as a potential treatment for humans, cell transplantation presents several technical and ethical complications. Nanoparticulate systems are a safe and effective method for introducing exogenous compounds into the brain. Therefore, we examined the effect of GDNF-conjugated nanoparticles microinjected into the striatum and nucleus accumbens on cocaine self-administration in rats. GDNF-conjugated nanoparticles blocked the acquisition of cocaine self-administration compared to control treatments. Furthermore, a cocaine dose response demonstrated that decreased lever response in rats that received GDNF-conjugated nanoparticles persisted after substitution with different cocaine doses. This effect is not due to a non-specific disruption of locomotor or operant behavior, as seen following a water operant task. The current study is one of the first demonstrations that drug-conjugated nanoparticles may be effective in treating brain disorders. These findings suggest that GDNF-conjugated nanoparticles may serve as a novel potential treatment for drug addiction.
Subject(s)
Brain/drug effects , Cocaine-Related Disorders/drug therapy , Cocaine/antagonists & inhibitors , Ferric Compounds/administration & dosage , Nanostructures , Nerve Growth Factors/administration & dosage , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain/metabolism , Brain/physiopathology , Cocaine/adverse effects , Cocaine-Related Disorders/physiopathology , Cocaine-Related Disorders/prevention & control , Conditioning, Operant/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/physiopathology , Disease Models, Animal , Dopamine/metabolism , Dose-Response Relationship, Drug , Drug Administration Routes , Glial Cell Line-Derived Neurotrophic Factor , Male , Microinjections/methods , Nanostructures/chemistry , Nanotechnology/methods , Nerve Growth Factors/chemistry , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Nucleus Accumbens/physiopathology , Rats , Rats, Sprague-Dawley , Self Administration , Treatment OutcomeABSTRACT
Administration of vaccinia immune globulin (VIG), derived from vaccinated healthy adult volunteers, is the treatment-of-choice for patients suffering from severe complications following smallpox vaccination. The present study was aimed to determine the time interval after vaccination, at which the highest titer of neutralizing antibodies is obtained. Ninety-nine 18-year-old soldiers, immunized with vaccinia virus at birth, participated in the study, 87 of whom had detectable antibodies against vaccinia virus prior to re-vaccination. Their initial average neutralizing antibodies titer (NT50) was 27. Fourteen days after re-vaccination the titer reached 152 and then dropped to 136, 119, 110 and 87 at 21, 30, 45 and 60 d, respectively. The titers of vaccinia antibodies induced in vaccinees without detectable antibodies at the start of the study, were significantly lower and the titers observed after re-vaccination were: 62, 56, 66, 38 and 34, at 14, 21, 30, 45 and 60 d, respectively. In an additional study, 65 volunteers vaccinated at birth and again at the age of 8 years old were re-vaccinated. Fourteen days later their NT50 was higher than those vaccinated only at birth. It can be concluded that bleeding of vaccinees 14 d following re-vaccination is the preferable time for the preparation of VIG.
Subject(s)
Antibodies, Viral/biosynthesis , Vaccination , Vaccinia virus/immunology , Adolescent , Follow-Up Studies , Humans , Immunization Schedule , Infant, Newborn , Kinetics , Neutralization Tests , Reference Values , RetreatmentABSTRACT
PURPOSE: The study was conducted to evaluate levels of anticomplement in seminal plasma and levels of complement in follicular fluid, in correlation with fertilization and pregnancy rate after in vitro fertilization and intracytoplasmic sperm injection programs. MATERIALS AND METHODS: Anticomplement levels were determined in 70 couples undergoing in vitro fertilization therapy. In 15 of these couples, complement levels were measured. Anticomplement and complement levels were also determined in an additional 21 couples (apart from the 70 couples) undergoing intracytoplasmic sperm injection treatment. RESULTS: A correlation was found between fertilization rate and anticomplement levels in the seminal plasma (r = 0.4, P < 0.01) after standard in vitro fertilization. No correlation was found in the intracytoplasmic sperm injection group, or observed between complement levels and any parameter examined in both groups. Pregnancy occurred only in those couples with an anticomplement:complement ratio below 0.49. CONCLUSIONS: Determination of anticomplement and complement levels may contribute to the assessment of a successful outcome of in vitro fertilization/intracytoplasmic sperm injection.
Subject(s)
Complement Inactivator Proteins/metabolism , Complement System Proteins/metabolism , Fertilization in Vitro , Follicular Fluid/chemistry , Pregnancy Outcome , Semen/chemistry , Female , Humans , Male , Microinjections , Pregnancy , Pregnancy Rate , Statistics as TopicABSTRACT
Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.
Subject(s)
Antibodies, Viral/analysis , Immunization, Secondary , Smallpox Vaccine/immunology , Smallpox/prevention & control , Variola virus/immunology , Adult , Humans , Male , Middle Aged , Neutralization Tests , Smallpox/immunology , Smallpox Vaccine/administration & dosage , Time FactorsABSTRACT
The correlation between skin reaction, exhibited by vaccinees immunized against smallpox, and antibody titer determined by plaque neutralization and ELISA, was evaluated. Twenty eight out of 35 young adults (vaccinated at infancy and at the age of 8 years), who were injected with vaccinia virus, displayed a major skin reaction a week later. An increase of four-folds and more, in antibody titer against vaccinia virus, is generally considered positive immunization take-up against smallpox. According to this criterion, only 17 of the vaccinees were found positive by plaque neutralization, while 25 by the indirect micro-ELISA. Thus, there were eight vaccinees who were considered immunized by the ELISA, (seven of them also according to the skin reaction), but not by the plaque neutralization test.