Review of novel particulate antigen delivery systems with special focus on treatment of type I allergy.

For the treatment of infectious diseases, cancer and allergy, the directed induction of an appropriate immune response is the ultimate goal. Therefore, with the development of pure, often very small proteins, peptides or DNA by molecular biology techniques, the research for suitable adjuvants or delivery systems became increasingly important. Particle formulations are made of a variety of materials, including lipids, proteins or amino acids, polysaccharides, polyacrylic substances or organic acids. Microparticles serve as vehicles and provide a depot for the entrapped or coupled antigen. The release occurs in a pulsatile or continuous manner, a feature, which is well controllable for many particulate systems. Particles attract antigen presenting cells to the administration site, thereby guaranteeing the efficient presentation of the antigen to the immune system. Importantly, particles also protect the entrapped substance. This is especially necessary after oral application to avoid gastric or tryptic breakdown. In this article, the design and construction of different antigen delivery systems and their immune effects, with special focus on the suitability for allergy treatment, are discussed.     

Synthesis and thermodynamic studies of two new polymers carrying amido and amino groups in the side chains

Two linear vinyl polymers carrying amido and primary amino groups in the side chains were synthesized and characterized. Their behaviour in aqueous solution was investigated by potentiometric, viscometric and calorimetric techniques. In both cases, the basicity constants show a linear dependence on the degree of protonation α, while the enthalpy values of protonation do not. The thermodynamic results demonstrate the important role of hydrophobic interactions on the protonation process.     

Ultrastructural changes in the blood-brain barrier after nimodipine treatment and induced hypertension

Fourty-four narcotized rats were split into two equal groups, one being treated with nimodipine and the other with a placebo. By use of norfenefrine the blood pressure was raised to values of 150 and 180 mm Hg within the limits of the autoregulation of brain perfusion and under continuous measurement. Fifteen minutes after application of the standard tracer, horseradish peroxidase, the animals were exsanguinated using a saline perfusion and then perfusion-fixed with Karnovsky's solution. After development of the peroxidase staining the brain sections were evaluated and then allocated to their respective groups. In brain tissues from the experimental group significantly more frequent perivascular accumulations of horseradish peroxidase reaction product were found (P less than 0.001). In electron micrographs it could be seen that the tight junctions were intact and that there was a neuroendothelial transport, with horseradish peroxidase-filled vesicles, in the endothelium, muscle cells, and brain parenchyma. These vesicles represent a medium of transport for all proteins of high molecular weight and can therefore result in brain edema. It is concluded that nimodipine damages the blood-brain barrier by disturbance of the autoregulation of the cerebral blood flow.     

Comparative anorexigenic activity and other pharmacological properties of quipazine and its N-acyl derivatives

In experiments on mice and rats quipazine exerts a moderate and short-term anorexigenic activity. N-acyl quipazine derivatives are markedly less toxic, do not exert anorexigenic action and influence weakly the serotoninergic and adrenergic systems.     

Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy

Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.     

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.     

Haloperidol treatments increased macrophage activity in male and female rats: influence of corticosterone and prolactin serum levels.

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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