Nanoparticle-Based Mucosal Vaccines Targeting Tumor-Associated Antigens to Human Dendritic Cells.

The induction of effective T cell-mediated immune responses is the main objective of vaccination against cancer. T cell responses are initiated by dendritic cells (DCs) as the most potent antigen-presenting cells. Designing vaccines for efficient delivery of tumor antigens to these cells in immunogenic fashion is, therefore, a major task in tumor immunology. In this human-based in vitro study we investigated the suitability of different polymeric nanoparticles (NPs) for delivering the tumor-associated antigen Her2/neu to DCs for induction of T cell responses by mucosal vaccination. The natural polymer chitosan and novel functionalized PLGA-based polymers were used for NP production. All NPs were efficiently taken up by DCs. Her2/neu delivered by NPs was more efficiently processed and presented by DCs than the soluble protein and induced more vigorous CD4+ and CD8+ T cell proliferation, and cytotoxic T cells. Testing the suitability of this platform for mucosal vaccination, NPs were applied to the apical side of an intestinal epithelium model and found to be efficiently transported across the epithelial layer to become available to basolateral DCs. Thus, chitosan and PLGA-based NPs are efficient carriers for delivery of antigens to DCs for induction of T cell-based immunity, and suitable for mucosal vaccine formulations.

Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity.

A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals. For the (68)Ga generator eluate concentration step, commercially available cation-exchange cartridges and (68)Ga generators were used. The (68)Ga generator eluate was collected by use of a strong cation exchange cartridge. 98% of the total activity of (68)Ga was then eluted from the cation exchange cartridge with 0.5 mL of 5 M NaCl solution containing a small amount of 5.5 M HCl. After buffering with ammonium acetate, the eluate was used directly for radiolabeling of DOTATOC and DOTATATE. The (68)Ga-labeled peptides were obtained in higher radiochemical purity compared to other commonly used procedures, with radiochemical yields greater than 80%. The presence of (68)Ge could not be detected in the final product. The new method obviates the need for organic solvents, which eliminates the required quality control of the final product by gas chromatography, thereby reducing postsynthesis analytical effort significantly. The (68)Ga-labeled products were used directly, with no subsequent purification steps, such as solid-phase extraction. The NaCl method was further evaluated using an automated fluid handling system and it routinely facilitates radiochemical yields in excess of 65% in less than 15 min, with radiochemical purity consistently greater than 99% for the preparation of (68)Ga-DOTATOC.

Copper(II) complexes of aminocarbohydrate beta-ketoenaminic ligands: efficient catalysts in catechol oxidation.

Copper(II) complexes of tridentate dianionic beta-ketoenaminic ligands derived from differently functionalized amino-deoxyglucoses were synthesized and characterized with respect to their structural, spectroscopic, and catalytic properties. The (probably dimeric) complex [1,2-O-isopropylidene-6-N-(3-acetyl-2-oxobut-3-enyl)amino-6-deoxyglucofuranoso)copper(II) Cu(3a) was a highly efficient catalyst for the catechol-oxidase-like oxidation of 3,5-di-tert-butylcatechol (dtbc) into 3,5-ditert-butylquinone (dtbq) by molecular oxygen (kcat=2.63s(-1)). In contrast to this magnetically "normal" complex Cu(3a), the analogous dinuclear complex [[Cu(2a)]2], derived from the isomeric amino sugar 5-amino-5-deoxyglucofuranose, forms six-membered chelate rings with the sugar moiety and has very strong antiferromagnetic-coupled copper atoms (resulting in a diamagnetic ground state). It has a rather insignificant activity (kcat < 10(-3)s(-1)). The ligand H2 1a, derived from a (protected) 6-amino-6-deoxyglucopyranose, forms a trinuclear complex [[Cu(1a)]]2.Cu(OAc)2] in which two basic formula units are bridged by one copper acetate. This compound and the complex derived from an (isomeric) aminodeoxyglucopyranose ([Cu(4a)]: kcat approximately equals 0.03 s(-1)) show moderate activity. All complexes with a peripheral ethoxycarbonyl group instead of the acetyl substituent R2, Cu(1b)-Cu(3b) and Cu(4c), are inactive. The complexes derived from 2-hydroxocyclohexylamine, Cu(5a) and Cu(5c), which were used as models of the active complex Cu(3a), have the typical "cubane-like" tetranuclear structure known from many copper complexes with derivatives of saturated 2-aminoalcohols. They are inactive with respect to the activation of dioxygen.

New Building Blocks for the Design of Oligonuclear Copper Complexes Based on Amino Carbohydrates.

Remarkably high magnetic coupling and O(2)-activation ability analogous to that of catechol oxidase are characteristics of the first structurally defined, low-symmetry oligonuclear copper complexes of tridentate beta-oxoenamine ligands based on amino carbohydrates (the structure of a bis(acetylbutenonylaminoglucosidato)bis(µ-acetato)tricopper(II) complex is shown).

[Not giving up prematurely. Rehabilitation instead of early pensions for officials with psychosomatic and addiction problems]. / Nicht zu früh aufgeben. Rehabilitation statt Frühpensionierung bei Beamten mit psychosomatischen und Suchtproblemen.

Many chances for a competent psychosomatic and dependence treatment for government employed people are still being overlooked. One-sided somatic fixation, premature urge for a permanent pension and indulgence are important contributing factors. There is, however, clear evidence that a sufficient in and/or out-patient treatment has a very favourable impact on the course of illness. The different therapeutic methods and their combination in a private psychosomatic hospital, which treats many government officials, are outlined and a clinical example is presented. Physicians in the public health sector are in the a singular position of helping to avoid premature pensioning and to keep the expenses caused by premature pensioning of people in government service low by means of informed and dedicated action.

[Continuous ambulatory peritoneal dialysis. 5-year clinical experience]. / Kontinuierliche ambulante Peritonealdialyse. Fünfjährige klinische Erfahrung.

Continuous ambulatory peritoneal dialysis (CAPD) is, next to conventional home dialysis, a world-wide method of treating chronic renal failure. This is the report of clinical experience of 34 CAPD patients who, from October 1978 to the end of 1983, had undergone 642 treatment months. The incidence of peritonitis after introduction of a new connector system in 1983 was reduced to 1 per 46 CAPD treatment months. In only 7 patients was it necessary to discontinue CAPD for reasons connected with the type of dialysis. No patient requested discontinuance of CAPD. Suitable bag and tube materials, adequate space, and well trained personnel are decisive for a successful CAPD programme, in addition to careful selection of patients. The latter aims at optimal patient motivation for the treatment method which, in principle, is more cost effective than home dialysis. In so far as patients fulfil the requirements for home dialysis they can be excellently rehabilitated.

[The possibility of pharmacologic therapy of extrapyramidal hyperkineses with tiapride]. / Pharmakologische Therapiemöglichkeit extrapyramidaler Hyperkinesen mit Tiaprid.

A novel substance, tiaprid (Tiapridex), from the family of the substituted benzamides, can be used in an attempt to block the dopaminergic receptors of the corpus striatum without inducing the psychiatric side effects on the mesolimbic system associated with, for instance, neuroleptics. Since hyperkinetic illness of the brain-stem ganglions accompanied by myoclonia, athetosis and dystonia are believed to stem from a state of imbalance between dopaminergic and cholinergic processes in which dopaminergic activity predominates, the application of tiaprid was tested on patients with etiologically different illnesses in an open clinical study. The course of treatment was documented by measurements and a record of clinical findings. No tolerance problems were encountered, and the substance had no grave side effects. Its effects proved to be good to very good on myoclonic hyperkinesis and good to moderate on athetosis, but dystonia seemed to be resistant to this form of treatment.

[The usefulness of dexamethasonephosphate in the conservative treatment of lumbar pain--a double-blind study (author's transl)]. / Uber den Wert der Anwendung von Dexamethasonphosphat in der konservativen Therapie der Lumboischialgie. Eine Doppeltblindstudie.

Analgesic drugs, physiotherapy and corticosteroids are concurrently used in the conservative treatment of lumbar pain. In 100 patients a double-blind study with dexamethasonephosphate versus placebo was performed. Lumbar pain and no findings with myelography were the basic requirements for inclusion into the study. There was no significant difference between the treatment group and the placebo group concerning the clinical investigation before and after treatment. The positive effect of dexamethasonephosphate, which was seen in a pilot study, was not confirmed in the double-blind study. Because corticosteroids are also psychotropic drugs there is a mild antidepressive effect. Considering the fact that cortisone has no effect on the symptoms of lumbar pain, it should not be used furthermore in the conservative treatment of lumbar pain.

Comparison of Doppler sonography and plate thermography for detection of carotid artery stenosis.

Foils coated with specific cholesterol esters indicate differences in temperature by changes in color. When these foils are placed on the skin, the skin temperature measured is related to the perfusion provided by the vessels supplying this area of the skin. A group of 300 patients were examined simultaneously with plate thermography and directional Doppler sonography in order to detect obstruction or occlusions of the carotid artery. Abnormalities were found in 42 patients. In 31, the positive findings obtained by the 2 methods were in agreement. In 8 only plate thermography gave a positive result, and in 3 only Doppler sonography yielded a relevant finding. Plate thermography as a method for the detection of a stenosis or an occlusion of the carotid artery is suggested as useful for an initial screening method.

[Medulloblastoma and pineoblastoma in monozygous twins (author's transl)]. / Medulloblastom des Kleinhirns und Pineoblastom bei eineiigen Zwillingen

Clinical and neuropathological findings in monozygous twin sisters are reported. Twin I died at age 5 months from a cerebellar medulloblastoma, whereas her sister died at age 16 months from a pineoblastoma. The tumors are considered similar referring to histogenesis, structural peculiarities and growth. Therefore, the twins are seen as concordant for the tumor type.