[Medicalization of social problems using the example of patients with pain]. / Medikalisierung sozialer Probleme am Beispiel von Schmerzpatienten.

The number of invalidity pensions for mental and psychosomatic disorders has dramatically increased in the last decade. Given the experience in sociomedical assessment of people with chronical pain diseases, we developed the impression that primarily social problems-especially long-term unemployment-play an important role in the processes of chronification of pain diseases. We evaluated 100 expert opinions from 2002-2007 according to quantitative and qualitative critieria. We found that at the time of applying for retirement nearly the whole sample was long-term unemployed and that the especially these people suffered from diseases characterized by pain at the beginning of their patient career and they all had received a large range of diagnostic and therapeutic interventions. Only during the course of their disease-usually after the rejection of their application for pension by expert medical opinions-did they receive the diagnosis in the field of psychiatry and psychosomatics. In a next step they were assessed by experts in the field of psychiatry and psychosomatics. In this article, the important social factors that influence this development are discussed.

The influence of garlic (Allium sativum) extract on interleukin 1alpha-induced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.

Inflammation plays an important role in both the initiation of atherosclerosis and development of atherothrombotic events. The adherence of leukocytes/monocytes to the endothelium is an early event in atherogenesis. Phytotherapeutica as garlic and garlic extracts were shown to have beneficial modulating effects in patients with atherosclerotic disease. The aim of this study was to evaluate in vitro the influence of water-soluble garlic (Allium sativum) extract on the cytokine-induced expression of endothelial leukocyte adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). Cytokine-induced expression of cellular adhesion molecules was measured on primary human coronary artery endothelial cell (HCAEC) cultures. HCAEC were cultured in microvascular endothelial cell growth medium and preincubated with garlic extract at various concentrations (0.25-4.0 mg/ml), after which human interleukin-1alpha (IL-1alpha, 10 ng/ml) was added for 1 day. Fluorescein isothiocyanate (FITC)-labeled anti-ICAM-1 and FITC-labeled anti-VCAM-1 were used to analyze the IL-1alpha-induced expression of ICAM-1 and VCAM-1 by flow cytometry. Incubation of HCAEC with garlic extract significantly decreased ICAM-1 and VCAM-1 expression induced by IL-1alpha. In addition, we examined the effects of garlic extract on the adhesion of monocytes to endothelial cells, using the monocytic U937 cell line. The presence of garlic extract significantly inhibited the adhesion of monocytes to IL-1alpha-stimulated endothelial cells. These results indicate that garlic extract modulates the expression of ICAM-1 and VCAM-1, thus potentially contributing to the beneficial effects traditionally attributed to garlic.

The effect of garlic on arteriosclerotic nanoplaque formation and size.

OBJECTIVE: In an in vitro biosensor model (PCT/EP 97/05212), the interplay between different lipoproteins in arteriosclerotic nanoplaque formation, as well as aqueous garlic extract (0.2-5.0 g/l from LI 111 powder) as a possible candidate drug against arterio/atherosclerosis were tested within the frame of a high throughput screening. METHODS: The processes described below were studied by ellipsometric techniques quantifying the adsorbed amount (nanoplaque formation) and layer thickness (nanoplaque size). A thorough description of the experimental setup has been given previously. RESULTS: Proteoheparan sulfate (HS-PG) adsorption to hydrophobic silica was monoexponential and after approximately 30 min constant. The addition of 2.52 mmol/l Ca2+ led to a further increase in HS-PG adsorption because Ca2+ was bound to the polyanionic glycosaminoglycan (GAG) chains thus screening their negative fixed charges and turning the whole molecule more hydrophobic. Incubation with 0.2 g/l aqueous garlic extract (GE) for 30 min did not change the adsorption of HS-PG. However, the following addition of Ca2+ ions reduced the increase in adsorption by 50.8% within 40 min. The adsorption of a second Ca2+ step to 10.08 mmol/l was reduced by even 82.1% within the next 40 min. Having detected this inhibition of receptor calcification, it could be expected that the build-up of the ternary nanoplaque complex is also affected by garlic. The LDL plasma fraction (100 mg/dl) from a healthy probationer showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+ concentration, with a strong increase at higher Ca2+ concentrations. GE, preferably in a concentration of 1 g/l, applied acutely in the experiment, markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca2+ concentrations used. In a normal blood Ca2+ concentration of 2.52 mmol/l, the garlic induced reduction of nanoplaque formation and molecular size amounted to 14.8% and 3.9%, respectively, as compared to the controls. Furthermore, after ternary complex build-up, GE similar to HDL, was able to reduce nanoplaque formation and size. The incubation time for HDL and garlic was only 30 min each in these experiments. Nevertheless, after this short time the deposition of the ternary complex decreased by 6.2% resp. 16.5%, i.e. the complex aggregates were basically resolvable. CONCLUSIONS: These experiments clearly proved that garlic extract strongly inhibits Ca2+ binding to HS-PG. In consequence, the formation of the ternary HS-PG/LDL/Ca2+ complex, initially responsible for the 'nanoplaque' composition and ultimately for the arteriosclerotic plaque generation, is decisively blunted.

["Medical expert assessment in psychosomatic and psychotherapy medicine--social justice questions" guideline]. / Die Leitlinie "Arztliche Begutachtung in der Psychosomatik und Psychotherapeutischen Medizin--Sozialrechtsfragen".

Guidelines on the medico-legal assessment of patients in the field of psychosomatics and psychotherapy prepared by the "German Society für Psychotherapeutic Medicine" is presented. These guidelines are based on published evidence and on expert consensus among psychotherapists, psychiatrists, judges and social security experts. They give a systematic overview on aspects relevant to the assessment of persons suffering from somatoform disorders, psychological factors in organic diseases and posttraumatic, anxiety, depressive, personality and eating disorders. These aspects are disability, severity, assessment of malingering, of disability and causality.

Chicken coagulation factor XIIIA is produced by the theca externa and stabilizes the ovarian follicular wall.

Development of the follicle in egg-laying species such as the chicken is regulated by systemic factors as well as by the highly orchestrated interplay of differentially expressed genes within this organ. Differential mRNA display analysis of defined phases of follicle development resulted in the characterization of coagulation factor XIIIA. It is expressed and produced by cells of the theca externa in a highly regulated manner during distinct growth phases of the follicle. Transcripts for factor XIIIA are already detectable at the beginning of follicle development and peak at the end of phase 2. Protein levels, however, still increase during phase 3, peak shortly after ovulation, and persist until the postovulatory tissue is completely resorbed. Factor XIIIA is secreted as a monomer into the extracellular matrix of the theca externa and is not associated with factor XIIIB as is the case in plasma. Our data suggest that, due to its transglutaminase activity, factor XIIIA stabilizes the follicular wall by cross-linking matrix components. Thus, coagulation factor XIIIA might play a key role in coping with the massive mechanical stress exerted by the large amount of yolk accumulating during the rapid growth phase of the oocyte.

Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.) are used for the treatment of mental depression, nervousness, sleeplessness and for their wound healing, diuretic and antirheumatic properties. As one biochemical mechanism for depression lack of catecholamine neurotransmitters has been discussed. The results of this investigation show that alcoholic extracts from Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine-beta-hydroxylase with an IC50 of 0.1 mu mol/l; pure commercial hypericin inhibits with an IC50 of 21 mu mol/l. Enzymes involved in the synthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by hypericin at concentrations from 1 up to 10 mu mol/l.

Biochemical activities of extracts from Hypericum perforatum L. 2nd Communication: inhibition of metenkephaline- and tyrosine-dimerization.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.), besides other activities such as wound healing, antigout, antirheumatic and diuretic properties, are widely used to counteract neurological disorders such as depressive situations, nervousness and sleeplessness. The characteristic and leading component in these extracts, the dianthraquinone hypericin, is very likely not to represent the main active principle mediating the desirable effects. Thus, standardization of the drug is no longer based on the quantification of total hypericin and since several years simply the determination of dry matter content is in use instead. As biochemical background of depression the lack of catecholamine neurotransmitters or decreased beta-endorphins such as methionine- or leucine-enkephalins have to be envisaged. This communication reports on the inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts. The substitution for enkephalins by tyrosine and for myeloperoxidase by horseradish peroxidase may represent a simple and inexpensive biochemical model reaction of pathological events during the manifestation of depressive events suitable for drug standardization.

Biochemical activities of extracts from Hypericum perforatum L. 3rd Communication: modulation of peroxidase activity as a simple method for standardization.

Alcoholic extracts from the herb "St. John's wort" (Hypericum perforatum L.) are widely used to counteract depressive situations, where the question on the mainly active principle is still under discussion. Thus, standardization of the drug on the basis of dry matter has been chosen instead of the popular leading component, hypericin. Inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts has recently been reported. This method is based on the separation and quantification of enkephalin dimers by HPLC. In order to simplify this assay myeloperoxidase could be substituted by the cheaper horseradish peroxidase and the enkephalins by the amino acid tyrosine without loss of significance. In this communication we represent a more rapid photometric method based on peroxidase-catalyzed indole acetic acid oxidation suitable for quick, simple and economic drug standardization.

Biochemical activities of extracts from Hypericum perforatum L. 4th Communication: influence of different cultivation methods.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.), know since ancient times as medical plant, besides other activities such as wound healing, antighout, antirheumatic and diuretic properties, is used in the treatment of mild to moderate depression. Increasing application continuously makes cultivation under controlled conditions of Hypericum perforatum L. more important. This report shows the results of three-years cultivation experiments with Hypericum perforatum L. The findings indicate that N-fertilizing yields more plant material but results in a drug with less quantity of secondary metabolites. Important components of the drug were quantified by HPLC and their activities were analyzed with the aid of biochemical test systems. Narrowleaved and broadleaved varieties of Hypericum perforatum L. show differences both in activity and quality. In this experiments the most active extract was a methanolic extract derived from non-fertilized, broadleaved plants.

Superoxide-dependent and -independent nitrite formation from hydroxylamine: inhibition by plant extracts.

Reactive oxygen species such as OH, peroxynitrite and the non-radical, hypochlorous acid, play outstanding roles in many disease. The formation of OH (Fenton)-type radicals is catalyzed by enzymes such as xanthine oxidase (XOD) via one-electron reduction of molecular oxygen producing superoxide radical anions (O2). Subsequent transfer of one electron to hydrogen peroxide by Fe2+ or Cu+ -ions yields OH-radicals measurable as ethene release from 1-keto-4-methylthiobutyrate (KMB). Xanthine oxidase or activated neutrophils are prominent sources of this strong oxidant produced at inflammatory sites. Many natural compounds such as salicylates or flavonoids interfere either with the production of these activated oxygen species or function as radical scavengers and thus as antioxidants. Extracts from willow-bark (Salix spec.) and also other species such as ash-tree (Fraxinus spec.) or poplar (Populus spec.) have been used as antiinflammatory drugs since a long time. In this communication we wish to report on model reactions to demonstrate a) the radical scavenging activities of such plant extracts inhibiting ethene release from KMB induced by Fenton-type oxidants and b) the inhibition of the formation of nitrogen monoxide (NO) from hydroxylamine including XOD either in the presence or absence of myoglobin (MYO) measurable as nitrite formation: In the absence of MYO, superoxide dismutase is an excellent inhibitor of nitrite formation but is inactive in its presence. Extracts from the willow-bark or the drug Phytodolar however, are inhibitory both in the presence and absence of MYO. As active principle, the flavonoid rutin included in these extracts is likely to function as one inhibitor of the XOD-mediated reaction.

Inhibition by Salix- extracts and Phytodolor of copper-catalyzed oxidative destruction.

Oxidation of low density lipoprotein (LDL) by copper ions is strongly inhibited by different aqueous extracts (Salix spec (SE); Fraxinus-Dolidago-Populus (Phytodolor)(PD) in a concentration range between 4 and 7 micrograms/ml. 10 to 50 microM salicylic acid (SA) stimulate LDL-oxidation whereas higher concentrations (10 to 500 micromM) showed no effect. Likewise ethene release from 2-keto-4-methylthiobutyrate (KMB) is strongly inhibited by the above extracts in a reaction driven by dihydroxyfumarate (DHF) in the presence of copper ions. This system may represent some features of the diabetic situation where DHF as an endiole may stand for certain Amadori products. In order to find out whether the inhibitory effects are due to copper chelation we tested the copper-dependent conversion of photodynamic ethane release from alpha-linolenic acid into ethene formation. Copper chelation is apparently only partially involved in inhibition of copper-dependent oxidations and only at a certain concentration of extracts from salix spec (SE) or extracts from Fraxinus-Solidago-Populus (Phytodolor)(PD).

Effect of magnesium pyridoxal 5-phosphate glutamate on vascular reactivity in experimental hypercholesterolemia.

Hypercholesterolemia is known to affect the responsiveness of various blood vessels to endogenous and to exogenous vasoactive agents. Of particular interest is the increased responsiveness to vasoconstrictors, e.g., 5-hydroxy tryptamine and noradrenaline, and the decreased reactivity towards vasodilators, e.g., acetylcholine. This, together with the development of arteriosclerosis, could play an important role in the progression of many vascular complications, such as hypertension and coronary heart disease. Magnesium pyridoxal 5-phosphate glutamate (MPPG) has been shown to effectively reduce serum lipids in animals and in man, and to retard the progression of atherosclerotic lesions in experimental animals. It was therefore considered of interest to investigate the reactivity of both the aorta and the renal artery to different vasoactive substances in hypercholesterolemic rabbits under the influence of MPPG as well as the effect of such substances on the blood pressure of the anesthetized animals. The rabbits were fed a high cholesterol diet for 2 months, followed by MPPG for 1 month, while keeping the rabbits on the same diet. One batch of animals was used for blood pressure recording and testing drug effects, and another was used for testing the responsiveness of their aortae and renal arteries to the different mediators. In hypercholesterolemic rabbits, treatment with MPPG tended to normalize the increased responsiveness of the blood pressure to the vasoconstrictors: noradrenaline and angiotensin and the diminished sensitivity to histamine and acetylcholine. For the isolated arteries, however, MPPG did not significantly affect the responses to noradrenaline nor potassium chloride, but tended to normalize responses to clonidine and acetylcholine. It could be concluded from the present findings that the high cholesterol diet induces changes in vascular reactivity which are possibly related to endothelial and/or receptor sensitivity changes. Treatment with MPPG helps to reverse these changes and to restore normal vascular reactivity, a fact that could have important clinical implications in the management of cardiovascular diseases.

Expression and conservation of apolipoprotein AIV in an avian species.

In birds, intestinally derived lipoproteins are thought to be secreted directly into the portal vein rather than to enter the circulation via the lymphatic system as in mammals. Hepatic clearance of these so-called portomicrons must be rapid, but the protein(s) mediating their catabolism, presumably analogues of the 36-kDa mammalian apolipoprotein E, have not been identified. In searching for such a mediator(s), we have isolated a hitherto unknown 38-kDa protein from chicken serum, which we identified by microsequencing and molecular cloning as a counterpart to mammalian apolipoprotein AIV (apoAIV). Mature chicken apoAIV consists of 347 amino acids, lacks cysteine residues, and displays 57% sequence identity with human apoAIV and, to a significantly lesser extent, with apoAIVs of rodents. This first nonmammalian apoAIV characterized is the smallest homologue reported so far, because of the lack of repeated motifs at the carboxyl terminus with the consensus sequence Glu-Gln-Glu/Ala-Gln, a hallmark of mammalian apoAIVs. Chicken apoAIV (isoelectric point, 4.65) is also considerably more acidic than its human counterpart. Agarose gel electrophoresis revealed that unlike human apoAIV, which migrates to a pre-alpha-position, chicken apoAIV shows fast alpha migration. Functional characterization demonstrated that the avian protein is able to activate the enzyme lecithin:cholesterol acyltransferase. Roosters and hens express apoAIV predominantly in the gut, one-fifth as much in the liver, and no other sites of expression are identifiable by Northern blot analysis. Although pronounced intestinal synthesis is common to apoAIVs, the features of the avian protein support the notion that it represents a prototype of an apoprotein that evolved to acquire possibly distinct functions in mammals and birds.

The carboxy-terminal two-thirds of the cowpea chlorotic mottle bromovirus capsid protein is incapable of virion formation yet supports systemic movement.

Previous investigations into recombination in cowpea chlorotic mottle bromovirus (CCMV) resulted in the recovery of an unusual recombinant virus, 3-57, which caused a symptomless infection of cowpeas but formed no detectable virions. Sequence analysis of cDNA clones derived from 3-57 determined that mutations near the 5' terminus of the capsid protein gene introduced an early translational termination codon. Further mutations introduced a new in-frame start codon that allowed translation of the 3' two-thirds of the capsid protein gene. Based on the mutations observed in 3-57, wild-type CCMV clones were modified to determine if the carboxyl two-thirds of the capsid protein functions independently of the complete protein in long-distance movement. Analysis of these mutants determined that while virion formation is not required for systemic infection, the carboxy-terminal two-thirds of the capsid protein is both required and sufficient for systemic movement of viral RNA. This indicates that the CCMV capsid protein is multifunctional, with a distinct long-distance movement function in addition to its role in virion formation.

[Functional treatment of diseases and injuries of the cervical spine]. / Die funktionelle Behandlung der Erkrankungen und Verletzungen der Halswirbelsäule.

The clinical findings and pain symptoms determine the functional treatment of the cervical spine disorders. Acute pain syndromes are to be approached by passive procedures, such as massage, electrotherapy, trigger point treatment. Could the pain reaction be reduced, the mobilizing techniques, including manipulation are indicated, followed by training therapy/reconditioning of shoulder girdle muscles. The patients are also to be instructed to perform home exercise program aiming the stabilization of cervical spine.

Effects of extracts from Populus tremula L., solidago virgaurea L. and Fraxinus excelsior L. on various myeloperoxidase systems.

Extracts from Populus tremula, Solidago virgaurea and Fraxinus excelsior are used as anti-inflammatory drugs. The effects of these extracts on myeloperoxidase (MPO), an enzyme liberated by activated granulocytes and known to produce the destructive agent hypochloric acid, were investigated. Populus and Fraxinus inhibited this enzyme, Solidago was without effect. These results were obtained concordantly with four different MPO-assays (H2O2/MPO; X/XOD/MPO; activated PMN; and elastase/alpha 1-PI-MPO). Fractionation of Populus and Fraxinus extracts showed that this inhibition is due to several different compounds. Well known or wide spread substances as e.g. rutin, salicylic acid, chlorogenic acid etc. had no or only little effect on the enzyme.

Severe musculoskeletal pain after cyclosporin A treatment in a patient undergoing allogeneic BMT.

Allogeneic BMT was performed in a 33-year-old man because of CML. Donor was his HLA-identical brother. GVHD prophylaxis consisted of short-term MTX and i.v. CsA. On day 17 cutaneous GVHD grade-III developed and high-dose methyl-prednisone was added. Initial daily dose of CsA was 4 mg/kg i.v. CsA dosage was adapted to maintain blood trough levels between 200 and 350 ng/ml. On day 27 the patient developed severe musculoskeletal pain of knees, legs, feet, hands, shoulders and ellbows. Only high-dose opioids and dextropropoxyphen were effective for analgesia. Additional medication besides CsA consisted of parenteral nutrition, steroids and antibiotics for total intestinal decontamination. Clinical and radiological examinantion revealed no causes for musculoskeletal pain. Serum levels for lactate-dehydrogenase, aldolase, alkaline-phosphatase, creatinphosphokinase with isoenzymes, electrolytes including magnesium were within normal ranges. Pain decreased within 4 days after switching, from intravenous to oral application. This case indicates that CsA in high dosage given intravenously combined with steroids can cause severe musculoskeletal pain as side effect in allogeneic BMT.

[The functional treatment of cervical spine disorders and trauma]. / Die funktionelle Behandlung der Erkrankungen und Verletzungen der Halswirbelsäule.

The clinical findings and pain symptoms determine the functional treatment of the cervical spine disorders. Acute pain syndromes are to be approached by passive procedures, such as massage, electrotherapy, trigger point treatment. Could the nocireaction be reduced, the mobilizing techniques, including manipulation are indicated, followed by trainingtherapy/reconditioning of shoulder girdle muscles. The patients are also to be instructed to perform home exercise program aiming the stabilization of cervical spine.

Sedative action of extract combinations of Eschscholtzia californica and Corydalis cava.

The herbal drug Phytonoxon N (abbreviated as PN) is indicated in nervousness induced insomnia, agitation and/or anxiety. It is composed of alcoholic drug extracts of the plants Corydalis cava (20%) and Eschscholtzia californica (80%). Both plants are rich in isoquinoline alkaloids derived from tyrosine metabolism. Recent research shows that they may influence the neurotransmitter metabolism.

Effects of ethanolic extracts from Eschscholtzia californica and Corydalis cava on dimerization and oxidation of enkephalins.

The endogenous pentapeptides, met-enkephalin and leuenkephalin, similar to their parent structures, beta-endorphin or dynorphin, bind to opioid receptors of the nociceptive system thus provoking analgesic responses. Peroxidases and phenolases (tyrosinase, catecholase) were shown to dimerize these pentapeptides thus possibly modulating their activity and/or lifetime. Extracts from plants from the order of the Papaverales contain isoquinoline alkaloids. Since the benzoisoquinolines are known to possess sedative-hypnotic activities, the potential effects of extracts from two species from this plant group, Eschscholtzia californica (Papaveraceae) and tyrosinase-catalyzed dimerization and/or oxidation of met-enkephalin were investigated. The results of the study show that the peroxidase-catalyzed dimerization via the tyr-residues is especially inhibited by the C. cava extract. The tyrosinase-catalyzed reaction yields five different products A-E, according to their HPLC-retention times. Consisting of the 4:1 (v/v) combination of the extracts from E. californica and C. cava, Phytonoxon N (abbreviated as PN) stimulates the formation of minor products A, B and E, whereas the formation of the major products C and D is inhibited. Only products C and D exhibit properties similar to the peroxidase-derived dimer. Product A is likely to be identical to DOPA-enkephalin.