Coffee's country of origin determined by NMR: the Colombian case.

The determination of the origin of coffee beans by NMR fingerprinting has been shown promising and classification has been reported for samples of different countries and continents. Here we show that this technique can be extended and applied to discriminate coffee samples from one country against all others, including its closest neighbors. Very high classification rates are reported using a large number of spectra (>300) acquired over a two-year period. As original aspects it can be highlighted that this study was performed in fully automatic mode and with non-deuterated coffee extracts. This is achieved using a series of experiments to procure a robust suppression of the solvent peaks. As is, the method represents a cost effective opportunity for countries to protect their national productions.

Altered oxytocinergic hypothalamus systems in sepsis.

Sepsis is known to affect neuroendocrine circuits: injections of lipopolysaccaride are potent stimulators of oxytocin secretion from the posterior lobe, acute sepsis leads to uterus contractions and spontaneous abort. Here, we report changes in expression and distribution of hypothalamic oxytocin in rats that had been subjected to caecal ligation and puncture which led to acute sepsis. Septic animals showed loss of oxytocin immunostaining in perikarya of the supraoptic and paraventricular nuclei and an increase of oxytocin positive fibres, suggesting a shift of oxytocin pools into the axonal compartment. Immunostaining of the posterior lobe revealed reduction of oxytocin in septic rats. Magnocellular neurons in supraoptic- and to a lesser extent in paraventricular nuclei showed nuclear immunoreactivity for the protooncogene c-Fos, indicating stimulation of transcriptional activity upon sepsis. Contrary to magnocellular oxytocin immunoreactivity, we observed increased oxytocin immunoreactivity in cell bodies and processes of periventricular nucleus and in perivascular neurons. Oxytocin neurons in other regions of the hypothalamus and the preoptic region did not appear to be affected by acute sepsis. Our findings suggest a differential activation of neurohypophyseal and cerebrospinal fluid contacting oxytocin systems while centrally projecting oxytocin neurons may not be affected. Systemic oxytocin levels may serve as additional diagnostic marker for sepsis.

["Fiction and Truth": Goethe's anatomical research at the University of Jena]. / "Dichtung und Wahrheit": Goethes anatomische Forschung an der Universität Jena.

Johann Wolfgang von Goethe was one of the most renowned German poets of the late Age of Enlightenment. However, his engagement went far beyond literature especially relating to politics and natural science. Goethe, primarily trained as a lawyer, developed his own theory of colors and even challenged the concepts of Isaac Newton. His discovery of the human intermaxilary bone questioned all the dogmas of the religious-minded world of the 18th century. Together with the anatomy professor Justus Christian Loder, Goethe performed comparative anatomy and proved the conceptual uniformity of humans and animals on 27 March 1784. Even though, Félix Vicq d'Azyr described the intermaxilary bone simultaneously in Catholic France, Goethe's findings were politically accepted due to the liberal Protestantism of the Duchy of Weimar. Nevertheless, leading anatomists of the century (Johann Friedrich Blumenbach, Petrus Camper and Samuel Thomas v. Soemmerring) mainly rejected Goethe's postulates which led to a delayed publication in 1820; almost 36 years after writing his original manuscript. Today, Goethe's discovery is known to be a fundamental basis for the development of Charles Darwin's theory of phylogenetic evolution. Nowadays, the Department of Anatomy contains the Museum Anatomicum Jenense which was founded by the Duke of Weimar, Carl August and Goethe and entails Goethe's premaxillary bones as its main attraction. The University values the cultural heritage of Goethe's contribution to Medicine and provides access to the collection to the public and generations of medical students. Still today Goethe's legacy is noticeable in the halls of the Alma Mater Jenensis.

Effect of repeated treatment with high doses of selegiline on behaviour, striatal dopaminergic transmission and tyrosine hydroxylase mRNA levels.

The anti-parkinsonian drug selegiline is a monoamine oxidase B (MAO-B) inhibitor and a potential neuroprotective agent which facilitates dopaminergic transmission. Its metabolites (-)-amphetamine and (-)-metamphetamine might contribute to the pharmacological effects as they are also able to increase dopaminergic transmission and in addition might lead to behavioural sensitization after repeated administration. We investigated the effects of acute and repeated treatment with a high dose of selegiline on dopamine overflow in the striatum as well as on behaviour and on tyrosine hydroxylase (TH) mRNA levels in midbrain. Two experiments were performed. In the first one, rats were implanted with microdialysis probes into the striatum and received daily injections of selegiline (10 mg/kg, i.p.) for 1 or 8 days or a single dose of saline. In vivo microdialysis was carried out on days 1, 8 or 17 (after withdrawal of 9 days) to measure dopamine overflow. Motility was measured at the same time. In the second experiment, rats were injected daily with selegiline (10 mg/kg, i.p.) or saline over a time period of 6 weeks or only once before the brains were processed for in situ hybridization with a (35)S-radiolabelled probe for TH. Repeated treatment led to higher levels in motility scores than acute administration after administration of the same dose, indicating behavioural sensitization, which was still manifest after an interruption of 9 days in the supply of selegiline. In contrast, acute administration of selegiline increased dopamine levels to a similar degree as the same dose after subchronic treatment, with or without interruption of 9 days. The dopamine metabolite DOPAC was reduced by more than 50% after acute administration of selegiline and even more so on day 8 by the same dose, after repeated administration. The basal concentrations of dopamine (before challenge with selegiline) were not altered by the repeated administration, whereas the basal concentrations of DOPAC were decreased by more than 80% by the repeated administration of selegiline, suggesting a decrease in dopamine turnover. Acute administration did not have any influence on TH mRNA levels, whereas chronic treatment significantly reduced TH mRNA levels in substantia nigra and ventral tegmental area. In conclusion, repeated administration of selegiline leads to behavioural sensitization independent of altered dopamine levels. In addition, it leads to a decrease, probably due to a down-regulation, of dopamine turnover and tyrosine hydroxylase.

Adaptive group sequential designs for clinical trials: combining the advantages of adaptive and of classical group sequential approaches.

A general method is presented integrating the concept of adaptive interim analyses into classical group sequential testing. This allows the researcher to represent every group sequential plan as an adaptive trial design and to make design changes during the course of the trial after every interim analysis in the same way as with adaptive designs. The concept of adaptive trial designing is thereby generalized to a large variety of possible sequential plans.

[Treatment of community-acquired lung abscess associated with aspiration]. / Therapie der ambulant erworbenen aspirationsassoziierten Lungenabszesse.

The management of community-acquired lung abscess associated with aspiration is based on adequate antimicrobial treatment and effective drainage. Empiric antimicrobial treatment should cover basic microbial patterns and consist of aminopenicillin/beta-lactamase-inhibitor or clindamycin. Since the spectrum of clindamycin is restricted to Gram-positive microorganisms combination treatment of clindamycin with a second-generation cephalosporin may be warranted. It is crucial to continue antimicrobial treatment until complete resolution of the abscess cavity and the corresponding infiltrates. Drainage is frequently present spontaneously. Additional techniques to ensure effective drainage include bronchoscopic and percutaneous drainage. These techniques are only infrequently indicated in case of clinical failure and of delayed cavity closure. Indications for surgical emergency interventions are mainly limited to severe pulmonary hemorrhage. The clinical success rate of adequate antimicrobial treatment together with effective drainage reaches 75 - 90 %.

Results of electrochemical therapy of colorectal liver metastases in rats followed up by MRI.

RATIONALE AND OBJECTIVES: Direct-current or electrochemical therapy is an alternative method for local tumor therapy. Until recently, it was mainly applied in China and was relatively unknown in the Western world. This study examines the feasibility and effectiveness of applying direct-current therapy in liver metastases of colorectal carcinomas in an animal model. METHODS: Liver metastases were implanted in 47 BDIX rats by subcapsular injection of cells from a colorectal strain (DHD/K12). The success rate of implantation and the size of the tumors were determined after 3 weeks by MR imaging (T2-weighted turbo spin-echo images; relaxation time 1,800 ms, echo time 80 ms). The direct-current therapy was applied by one platinum electrode placed in the center of the tumor and four at the periphery of the tumor. Suitable therapy parameters were established in a pilot study by comparing four different methods of direct-current therapy with a control group. The methods varied with respect to the electrode polarity and the applied voltage. In a second series of investigations, tumor growth was monitored by MR imaging 3 and 5 weeks after therapy. RESULTS: The tumor implantation rate was 92.6% at a tumor cell concentration of 8 x 10(5)/mL. The most effective therapy method was achieved by placing an anode at the center of the tumor and four cathodes at the periphery, with an applied charge of 80 C/cm3. Complete tumor necrosis was observed in 54% of cases. In the follow-up measurements, the mean tumor diameter was 0.65 cm at 3 weeks after therapy and 0.76 cm at 5 weeks after therapy. In comparison with the control group (1.08 and 1.53 cm, respectively), this represented a significant reduction in tumor growth rate. CONCLUSIONS: This study is the first to demonstrate an antitumoral effect of direct-current therapy on liver metastases of colorectal cancer in rats.

T-cell-activating monoclonal antibodies, reacting with both leukocytes and erythrocytes, recognize the guinea pig Thy-1 differentiation antigen: characterization and cloning of guinea pig CD90.

A glycophosphatidylinositol (GPI)-linked differentiation antigen expressed on guinea pig T and B lymphocytes was identified by several monoclonal antibodies; it has been shown previously that this membrane protein induced strong polyclonal T cell proliferation upon antibody binding and costimulation by PMA. Purification by immunoadsorption and microsequencing revealed that this T-cell-activating protein is the homologue of Thy-1 or CD90. In contrast to the Thy-1 antigen of most other species, guinea pig Thy-1 has a much higher molecular weight, which is due to a more extensive N-linked glycosylation, bringing the molecular weight of the total antigen up to 36 kDa. Molecular cloning of guinea pig Thy-1 indicated that the deduced molecular weight of the protein backbone is 12,777 after removal of an N-terminal 19-amino-acid leader peptide and cleavage of the 31 amino acids for GPI anchoring the C-terminal end. Sequence comparison showed that guinea pig Thy-1 has an 82% homology to human and a 72% homology to mouse Thy-1 on the amino acid level. Immunohistological staining of cryostat sections revealed intensive staining with the monoclonal antibody H154 on fibroblasts, fibrocytes, Kupffer cells, alveolar macrophages, and mesangial cells. As observed in the human, mouse, and rat, Thy-1 is abundant in the guinea pig brain. Unlike Thy-1 expression in other species, guinea pig Thy-1 is strongly expressed on most resting, nonactivated B cells and, to a lesser extent, on erythrocytes. While treatment of erythrocytes and lymphocytes with GPI-specific phospholipase C largely decreased reactivity with mAb H154, T cells retained the proliferative response to antibody and phorbol esters.

Drug addiction therapy. A dance to the music of time.

Dance therapy can play a useful role in the treatment and rehabilitation of women with drug addiction. It works by raising self-esteem through an improved relationship with the body, giving women the strength to help combat their habit. The benefits of dance therapy for women at the detox unit of Holloway Prison have been confirmed by prison staff.

[Direct-current treatment of chemically induced mammary carcinoma in an animal model: MR volumetric assessment of the effect of the therapy]. / Gleichstrombehandlung des chemisch induzierten Mammakarzinoms im Tiermodell: MR-volumetrische Erfassung des Therapieeinflusses.

PURPOSE: To investigate the effect of direct current treatment (DCT) on the growth of mammary carcinomas in rats by MR-volumetry. METHODS: Chemically induced mammary adenocarcinomas in a control group (n = 17) were compared with treated tumours (18 C/cm3 in group A: n = 7 or 36 C/cm3 in group B: n = 12). 31 untreated tumours were situated near a treated tumour (group C). Experiments were carried out using one positive electrode in the tumour centre and three negative electrodes in the periphery. The tumour volume was measured by MRI before, and 1, 3, 6, 9 and 12 weeks after treatment. RESULTS: 12 weeks after DCT, the mean tumour volume in group A (164% +/- 158%, p < 0.05) and group B (13% +/- 24%, p < 0.001) was significantly reduced compared to the control group (434% +/- 230, Mann-Whitney U-Test). Complete tumour regression occurred in 42% of tumours in group B and was not achieved in group A, C and control group. Tumour growth in group C was decreased compared to the control group. CONCLUSIONS: The effectiveness of DCT was found to depend on the applied dosage -36 C/cm3 was more effective than 18 C/cm3. The effect of DCT is not limited to the area between the electrodes.

[Interim analysis of a prospective, randomized multi-center study by the "Liver Metastases" Study Group: adjuvant intra-arterial chemotherapy after curative liver resection of colorectal metastases]. / Interimsanalyse einer prospektiven, randomisierten Multizenterstudie der Arbeitsgruppe "Lebermetastasen": Adjuvante intraarterielle Chemotherapie nach kurativer Leberresektion kolorektaler Metastasen.

Recurrence after resection of colorectal liver metastases occurs after 9-12 months in up to 80% of patients. Half of the relapses is isolated to the liver. An intraarterial chemotherapy with 5-FU and folinic acid was compared to only resection. Main objective of the trial was survival. Within 14 days after resection followed the 6-month therapy with 5-FU 1000 mg/m2 continuously over 5d/28d and Folinic Acid 200 mg/m2 over 15 minutes 5d/28d. The first interim-analysis with 226 randomised patients showed in the intention-to-treat-analysis a median survival of 34.5 months (m.) with therapy versus 40.8 months (p = 0.1519 with a negative trend. (95%-Confidence interval for hazard ratio: [0.5; 1.15]) and time to progression of 14.2 m. with therapy versus 13.7 m. Severe toxicities (WHO grade III/IV) occurred in 25.6% of cycles and 62.9% of patients. Mainly registered were stomatitis (57.6%) and nausea (55.4%). The recruitment of patients for study was terminated, because in best case the risk to die could be lowered only by 15% and therefore clinical relevant prolongation of survival is not to achieve with this type of adjuvant therapy.

[Pilot study of effectiveness of electrotherapy in the experimental liver metastasis model]. / Pilotstudie zur Wirksamkeit der Gleichstromtherapie im experimentellen Lebermetastasenmodell.

The aim of the present was to assess the effectiveness of low level direct current therapy in liver metastases and the influence of polarity (anode or cathode in the center of the tumor) or current dose (60 or 80 C/cm3). Colorectal metastases were established in 25 BD IX rats by injection of DHD/K12 colon cancer cells under the liver capsule. After 3 weeks the tumors were treated by low level direct current therapy (applied with five platinum electrodes). Histological examination of the removed livers on postoperative day 7 revealed significant destruction of the metastases with localized necroses. The best treatment results were obtained in the group with an anode in the center and a current dose of 80 C/cm3. We conclude that low level direct current therapy may offer an alternative minimal invasive method in the treatment of liver metastases.

Enrichment of G protein alpha-subunit mRNAS in the AV-conducting system of the mammalian heart.

We investigated the expression pattern of the heterotrimeric G proteins Gs alpha, Gi alpha-2 and Go alpha in rat and guinea-pig heart by in situ hybridization. Cryosections were hybridized with single-stranded 35S-cRNA probes complementary to subtype-specific sequences of the respective mRNAs. Hybridization signals were visualized by exposition to X-ray films and dipping autoradiography. The rank order of abundance was Gi alpha-2 approximately Gs alpha >> Go alpha. In general, G protein alpha-subunit mRNAs were evenly distributed in the heart including endo- and epicardium, large vessels and valves. Go alpha-mRNA levels were significantly higher in atria than in ventricles. In contrast to the rather uniform labeling of working myocardium, expression of all three G proteins was enriched in small intramural blood vessels and in subendocardial Purkinje fibers of septum and papillary muscles. A more marked enrichment of Gs alpha-, Gi alpha-2- and especially Go alpha-mRNA was seen in neuronal ganglionic cells in the atrial septum and posterior regions of the atrium. The main finding, however, was an enrichment of all three G protein mRNAs in the atrioventricular conductive tissue. The accumulation was strictly co-localized with acetylcholinesterase-positive regions identified as the atrioventricular node, the bundle of His and the right and left bundle branches and was seen similarly in rat and guinea-pig hearts. Quantitative in situ hybridization revealed Gs alpha-, Gi alpha-2- and Go alpha-mRNA levels in the bundle of His to be 206 +/- 0.13%. 191 +/- 0.15% and 165 +/- 0.06%, respectively, of that in the surrounding interventricular working myocardium. These findings indicate that heterotrimeric G proteins play an important role in modulation of electrical conductance in the heart.

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.

Modulation of key reactions of the catecholamine metabolism by extracts from Eschscholtzia californica and Corydalis cava.

Aqueous-alcoholic extracts from Eschscholtzia californica inhibit the enzymatic degradation of catecholamines as well as the synthesis of adrenaline, whereas aqueous-ethanolic extracts from Corydalis cava enhance the chemical oxidation of adrenaline and the synthesis of melanine from dihydroxyphenylalanine (DOPA). Both extracts dramatically shorten the lag phase in the catalysis of phenolase probably due to their o-diphenol content, where the Corydalis extracts are 10 times more active than the Eschscholtzia preparations. Dopamine beta-hydroxylase and monoamine oxidase (MAO-B) are especially inhibited by Eschscholtzia extracts. Diamine oxidases are inhibited by both preparations to a similar extent. The results of this study may be interpreted as a cooperative function of the two preparations in establishing and preserving high catecholamine levels thus explaining their sedative, antidepressive and hypnotic activities.

Flavonoids from Leptospermum scoparium with affinity to the benzodiazepine receptor characterized by structure activity relationships and in vivo studies of a plant extract.

The New Zealand Myrtacea Leptospermum scoparium Forst. contains lipophilic flavonoids which interact specifically with benzodiazepine receptors. For an indepth characterization of their binding behavior, structure activity relationships were delineated which are in accord with results obtained by quantum-chemical and spectroscopic methods. Inhibition experiments have been performed by a radio receptor assay with [3H]flunitrazepam and IC50-values of 2.1 microM for 5,7-dimethoxyflavone (1), 45 microM for 5,7-dimethoxy-6-methylflavone (2), 3.3 microM for 5-hydroxy-7-methoxy-6-methylflavone (3) and 40 microM for 5-hydroxy-7-methoxy-6,8-dimethylflavone (4) have been measured. Flavanones 5 to 8, however, at concentrations < or = 0.1 mM, did not show a 50% inhibition of the binding radiolignand. The agonistic profile of the flavones was determined indirectly by TBPS-shift experiments which revealed a negative cooperation with the TBPS/picrotoxinin-binding site. To characterize the biologically active conformations, energy minima were calculated using the semiempirical method AM1. The steric arrangement of the substituents for all global minima calculated were in accord with homonuclear NOE-experiments. A correlation of the geometry of the lowest energy conformers with corresponding IC50-values reveals an increase of the affinity towards the benzodiazepine receptor, when the substituents at the flavones are coplanar to the aromatic system and R3 represents a sterically demanding methylgroup. Analyses of the global minima of 5,7-Dimethoxyflavone and diazepam showed one conformer each, in which the methoxy substituent in R3 and the N-methyl on the one hand and the corresponding carbonyl oxygens as well as the unsubstituted phenyl rings on the other were nearly superimposable. The flavanones lacking the double bond between C-2 and C-3 have angular structures, whereby the loss of affinity to the receptor can be explained. From the locomotion study with rats, an in vivo sedating, possibly even anxiolytic effect of the dry extract of the tincture prepared from Leptospermum scoparium by use of 70% ethanol, could be concluded. At doses of 50 mg and 250 mg of the dry extract per kg of body weight, an unequivocal but not linear dose-activity relationship in respect to the moving activities of the animals was determined. Upon an application of 500 mg of this extract per kg body weight, by contrast, only a negligible reduction of the moving activity was found in relation to a control group. We suppose that at higher doses, activating compounds of the extract come to the fore pharmacologically neutralizing the primarily sedating effect.

[Which patients benefit from treatment with respiratory feedback?]. / Welche Patienten profitieren von einer Behandlung mit dem respiratorischen Feedback (RFB)?

The physiological and psychological data of 82 patients with essential hypertension, who participated in the treatment group of a respiratory feedback (RFB) evaluation (Franck et al. 1994), were examined, using clusteranalysis, to detect and to describe therapy responders and nonresponders. For patients with usual personality characteristics, active coping strategies and interest in games and technics the best blood-pressure decrease (systolic bp: 13.05 mmHg, diastolic bp: 10.63 mmHg) was found. Furthermore patients, who stopped RFB-treatment have been compared with patients, who finished the treatment program. Patients, who stopped the RFB-treatment, had more psychological symptoms in the sense of psychosomatic complaints.

[Relaxation therapy with respiratory feedback in patients with essential hypertension]. / Entspannungstherapie mit dem respiratorischen Feedback bei Patienten mit essentieller Hypertonie.

During a stationary rehabilitation program for four to six weeks 170 patients with essential hypertension participated in a respiratory feedback (RFB) evaluation. 91 patients were treated with this relaxation therapy and compared with 79 controls. Furthermore the anti-hypertensive medication was controlled. One treatment group (without antihypertensive medication) had a higher systolic blood-pressure decrease than controls. In both treatment groups psychological effects in the sense of more positive mood and less physical complaints were found.