Immune responses in mice of beta-galactosidase adsorbed or encapsulated in poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres.

The immune response induced in mice by beta-galactosidase (beta-gal) adsorbed or encapsulated on poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres was investigated. The encapsulated protein elicited higher antibody response than the protein adsorbed on the microspheres in the case of the PLA microspheres. However, the encapsulated protein elicited weaker antibody response than the adsorbed protein in the case of the PLGA (50:50) microspheres, probably because, in this case, the encapsulation process adversely affected protein immunogenicity. In the case of adsorbed beta-gal, higher antibody response was obtained with the PLA microspheres than with the PLGA (50:50) microspheres. This may be related to the lower rate of beta-gal desorption from the PLA microspheres. Based on the immunoglobulin G1/immunoglobulin G2a ratios and the stimulation indices for interferon-gamma and interleukin-4, beta-gal encapsulated or adsorbed on PLA microspheres induced a Th(1)-biased immune response whereas beta-gal encapsulated or adsorbed on PLGA (50:50) microspheres induced a Th(2)-biased immune response. The results obtained indicate that more potent immune responses are obtained when the protein is encapsulated than adsorbed on the microspheres, providing that the encapsulation process does not adversely affect protein immunogenicity. Also, the type of polymer used to prepare the microspheres, but not the method of protein association with the microspheres, may affect the type of immune response.

PLA and PLGA microspheres of beta-galactosidase: Effect of formulation factors on protein antigenicity and immunogenicity.

The entrapment of beta-galactosidase (Escherichia coli) in PLA and PLGA microspheres using a double emulsion technique resulted to significant reduction of protein antigenicity. The extent of antigenicity loss depended on the conditions of microsphere preparation. Most of antigenicity loss occurred on the first emulsification step. Only the effects of microsphere preparation factors having an important influence on protein antigenicity, such as the type of organic phase (polymer solvent) and homogenization, could be predicted (on a qualitative basis) by antigenicity data obtained after the first emulsification step. The type of polymer and polymer solvent used to prepare the microspheres affected beta-galactosidase immunogenicity. The PLA microspheres prepared using ethyl acetate was the most immunogenic microsphere formulation, eliciting similar total antibody responses as the alum formulation of beta-gal. This formulation was the only microsphere formulation that induced an IgG1/IgG2a ratio lower than 1, indicating an immune response biased towards a Th1 type. The results obtained indicate that large protein molecules with complex tertiary structure such as beta-galactosidase can be entrapped in PLA and PLGA microspheres with retention of protein immunogenic potential, providing that appropriate conditions of microsphere preparation are applied, and that the formulation of microspheres might influence the Th1/Th2 type of immune response against the encapsulated antigen.

Evaluation of psychiatric morbidity following an earthquake.

Greece has been characterized by high earthquake activity in comparison not only with Mediterranean countries, but also with many parts of Eurasia. In the present study an assessment of the psychiatric morbidity was carried out in the city of Kalamata, Greece, two weeks after the earthquake in September, 1986. A random sample of residents divided into three categories was assessed. The participating groups consisted of 205 adults, 172 high school students and 69 adult outpatients who suffered from minor pathological problems or proceeded for a check-up without being necessarily ill. The Langner and CES-D scales were administered for the population assessment. Detailed statistical analysis revealed that the earthquake had significant psychological effects and caused a considerable degree of depression in all groups. According to the Langner Scale, 31.3% of the general population, 11.6% of the students and 40.6% of the patients exhibited 10 or more symptoms on the Langner scale indicating severe disturbance. Also 50.9% of the whole sample exhibited 6 or more symptoms indicating serious disturbance. In the CES-D scale, 79% of the general population, 69.2% of students and 75% of the outpatients exhibited 16 or more symptoms, or 74.6% of the whole sample. The observed difference between general population and students is significant on Langner scale (p less than 0.001) and on CES-D scale (p less than 0.025). The major symptoms in all groups were prevalence of severe psychiatric symptomatology, anxiety, psychosomatic disorders and depression.