Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients.

BACKGROUND: According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS: Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS: Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS: The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

Trends in surgery and outcomes of squamous cell vulvar cancer patients over a 16-year period (1998-2013): a population-based analysis.

PURPOSE: The objective was to identify trends in surgery and the outcomes of squamous cell vulvar cancer in a population-based setting. METHODS: A total of 1113 patients with squamous cell vulvar cancer diagnosed between 1998 and 2013 in the catchment area of the Munich Cancer Registry (population approximately 4.6 million) were analysed. Trends in prognostic factors and treatment were examined by comparing patients diagnosed between 1998 and 2008 with those diagnosed between 2009 and 2013. Cumulative incidence was used to calculate time to local (LR) and lymph node recurrence (LNR). Survival was analysed by the Kaplan-Meier method, calculation of relative survival (RS), and a Cox model. RESULTS: The high median age at diagnosis of 75 years did not change significantly over time. In addition, no changes in the subsite of tumour or grading were noted. A decrease in patients undergoing complete vulvectomy from 27.7 to 17.8 % (p < 0.001) as well as an increase in the use of sentinel lymph node biopsy from 11.4 to 39.1 % (p < 0.001) was observed. However, time to LR (from 19 to 19 %) and time to LNR (from 9 to 9 %) as well as 5-year overall survival (from 55 to 55 %) and RS (from 66 to 63 %) were not significantly altered. After adjustment for prognostic factors, less radical locoregional surgery had no influence on survival. CONCLUSION: Less radical locoregional surgery in vulvar cancer is increasingly implemented. Locoregional recurrence and survival have not been affected by these changes and are likely accompanied by an improvement in quality of life.

['Walkability' and physical activity - results of empirical studies based on the 'Neighbourhood Environment Walkability Scale (NEWS)']. / 'Walkability' und körperliche Aktivität - Stand der empirischen Forschung auf Basis der 'Neighbourhood Environment Walkability Scale (NEWS)'

OBJECTIVE: 'Walkability' is mainly assessed by the NEWS questionnaire (Neighbourhood Environment Walkability Scale); in Germany this questionnaire is widely unknown. We now try to fill this gap by providing a systematic overview of empirical studies based on the NEWS. METHODS: A systematic review was conducted concerning original papers including empirical analyses based on the NEWS. The results are summarised and presented in tables. RESULTS: Altogether 31 publications could be identified. Most of them focus on associations with the variable 'physical activity', and they often report significant associations with at least some of the scales included in the NEWS. Due to methodological differences between the studies it is difficult to compare the results. CONCLUSION: The concept of 'walkability' should also be established in the German public health discussion. A number of methodological challenges remain to be solved, such as the identification of those scales and items in the NEWS that show the strongest associations with individual health behaviours.

[Association between the social status of city districts and health risks: multilevel analyses concerning the regional distribution of overweight, hypertension and self-rated health in Augsburg, Germany]. / Zusammenhang zwischen dem sozialen status eines stadtgebietes und den gesundheitlichen risiken seiner bewohner: ergebnisse einer mehrebenenanalyse zu übergewicht, hypertonie und gesundheitszustand am beispiel Augsburg.

INTRODUCTION: In empirical studies it has repeatedly been shown that the socioeconomic status (SES) of a region could infl uence the health status of its inhabitants, even if measures of individual SES are controlled for. This research has just started in Germany, but most studies focus on large geographical areas such as rural districts. Taking the example of districts in the city of Augsburg, the analyses focus on the question if these associations can also be found in a small-scale regional comparison. METHODS: We included 1 888 participants of the KORA S4 Survey aged 25-74 years. The city districts were grouped according to the unemployment rate (low, medium, high). The dependent variables were self-rated health and 3 risk factors (obesity, high waist-hip ratio, hypertension). Additional individual variables included are age, sex, educational level and unemployment. The analyses were based on multilevel logistic regressions. RESULTS: After adjustment for individual level variables (age, sex, education, unemployment), the analyses show a signifi cantly increased risk of 'high waist-hip ratio' in the regions with the highest unemployment rate (OR 1.53; 95 % conf. interval 1.03-2.26). A similar association was found for obesity. No signifi cant association was observed between unemployment rate on the one hand and hypertension and self-rated health on the other. CONCLUSION: Some health risks seem to be especially high in city districts characterised by a high unemployment rate. It can be concluded that interventions aimed at reducing these risks should focus on districts with high unemployment rates. Further studies are needed for an understanding of the causes behind the social and regional inequalities shown here.

The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.

The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitro assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensi mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparum transmission stages.

Thrombin-antithrombin complex and the prothrombin fragment in arterial and venous blood of patients with peripheral arterial disease.

BACKGROUND: Thrombin generation has recently been recognized as an important factor in the development of arterial occlusive disease in all vascular provinces. Several reports concerning markers of thrombin generation have been published with however, conflicting results. It has been demonstrated in vitro that accelerated blood flow velocity causes increased thrombin generation via higher shear rates. In recent articles TAT and F1 + F2 concentrations are reported significantly higher in arterial than in venous blood. A correlation with the severity of atherosclerosis or specially with the stage of PAD was expected. In the present investigation we additionally collected blood from the femoral vein. PATIENTS AND METHODS: In 11 patients with Fontaine stages IIb to IV and two healthy subjects TAT and F1 + F2 concentrations were determined in blood samples from the femoral artery, the femoral vein (diseased leg) and cubital vein. In all cases and at all puncture sites exactly the same atraumatic technique of venipuncture was used. RESULTS: The concentrations of TAT and F1 + F2 were significantly elevated in patients with PAD. There was no significant difference between the concentrations of TAT and F1 + F2 in arterial (femoral artery) and venous (femoral vein and cubital vein) blood. CONCLUSION: The results from previous investigations have been confirmed only partially. Differences in the puncture techniques to collect arterial or venous blood result in an increased scattering of the data and a systematic error.

A screen in Saccharomyces cerevisiae identified CaMCM1, an essential gene in Candida albicans crucial for morphogenesis.

Morphogenesis in Saccharomyces cerevisiae and the pathogenic yeast Candida albicans is governed in part by the same molecular circuits. In S. cerevisiae, FLO11/MUC1 expression has been shown to be modulated by multiple signalling pathways required for pseudohyphal development. We have established a screen in S. cerevisiae to identify regulators of fungal development in C. albicans based on FLO11::lacZ expression as a reporter. This screen identified both known components of the mitogen-activated protein kinase (MAPK) cascade and the cAMP cascade that are important for hyphal development in C. albicans, as well as genes not yet known to be involved in morphogenesis. The Candida homologue of MCM1 is one of the novel factors identified in this screen as being important for morphogenesis. CaMcm1p levels do not vary significantly in different cell types and respond to an autoregulatory feedback mechanism, arguing that CaMcm1p activity is regulated by post-translational modifications. Both overexpression and repression of this essential gene led to the induction of hyphae. Moreover, we found that the expression of HWP1, a hyphae-specific gene, was induced by repression of CaMCM1. The changes in morphology and HWP1 expression were not the result of a change in expression levels of NRG1 or TUP1, known repressors of hyphal development. Thus, CaMcm1p is a component of a hitherto unknown regulatory mechanism of hyphal growth.

Impaired immunoglobulin M production by incubation of hybridoma cells with ethanol.

Several reports have presented results that demonstrate suppression of the immune system by ethanol. Using a hybridoma cell model, we studied the effects of ethanol on cell proliferation and on the production of immunoglobulin M (IgM) antibodies. The number of cells decreased while incubated with as little as 25 mM ethanol but not in a clonal subline incapable of IgM production, indicative of an increased vulnerability associated with the antibody-producing machinery. Levels of antibodies in cell culture supernatants were monitored by -heavy-chain-specific and -light-chain-specific enzyme-linked immunosorbent assays. We found a significant decrease in antibody concentration at 200 mM ethanol compared with findings for nonexposed cells. In addition, lower -chain compared with -chain values were monitored at ethanol concentrations of 50 mM and higher. This difference suggests irregular composition of the antibodies in the supernatant. Determination of IgM levels within the hybridoma cells revealed a linear increase in antibody concentrations by as much as three times the control levels with increasing ethanol concentrations when correlated with cell numbers. Analysis of the mRNA levels of two ethanol-inducible stress proteins, the 78-kilodalton glucose-regulated protein (GRP78) and the 70-kilodalton heat-shock protein (HSC70), by quantitative Northern hybridization yielded increased mRNA in a nonlinear fashion. The results demonstrate that ethanol impairs IgM composition, whereas antibody production within hybridoma cells is increased and the assembling machinery is activated, indicating compensating processes.

[Lymph node metastasis in head-neck tumors]. / Lymphknotenmetastasierung bei Kopf-Hals-Tumoren.

BACKGROUND: One of the most important criteria of malignancy of head and neck cancer are the cervical lymph metastases. Being significant for the therapeutical plan is how tumor depending parameters like T-stage, degree of differentiation and tumor localisation will influence the N-stage and therefore the extension of neck dissection. METHOD: To evaluate the pattern of formations of metastases and the success of therapy a retrospective study was performed on 405 patients with carcinoma of the oral cavity (n = 47), the oropharynx (n = 117), the hypopharynx (n = 47) and the larynx (n = 193). RESULTS: By the time of surgery carcinoma of the hypopharynx were most frequently accompanied by cervical metastases (80%), followed by carcinoma of the oropharynx (70%), the oral cavity (52%) and the larynx (26%). Occurrence and extension of regional lymph node metastases correlated well with T-stages and degree of differentiation. After surgical therapy locoregional recurrence could be observed in 5.2% of the patients. Five-year-survival rate was reduced to 50% on patients with positive lymph nodes. The different tumour sites showed preferred patterns of metastatic spread, without complete avoidance of certain levels. CONCLUSION: For the decision on indication and extent of neck dissection the preoperative diagnostic (ultrasound, CT-scan, MRI), localisation of tumour, T-stage, degree of differentiation and the knowledge of typical metastatic spread must be considered.

The loop region covering the iron-sulfur cluster in bovine adrenodoxin comprises a new interaction site for redox partners.

The amino acid in position 49 in bovine adrenodoxin is conserved among vertebrate [2Fe-2S] ferredoxins as hydroxyl function. A corresponding residue is missing in the cluster-coordinating loop of plant-type [2Fe-2S] ferredoxins. To probe the function of Thr-49 in a vertebrate ferredoxin, replacement mutants T49A, T49S, T49L, and T49Y, and a deletion mutant, T49Delta, were generated and expressed in Escherichia coli. CD spectra of purified proteins indicate changes of the [2Fe-2S] center geometry only for mutant T49Delta, whereas NMR studies reveal no transduction of structural changes to the interaction domain. The redox potential of T49Delta (-370 mV) is lowered by approximately 100 mV compared with wild type adrenodoxin and reaches the potential range of plant-type ferredoxins (-305 to -455 mV). Substitution mutants show moderate changes in the binding affinity to the redox partners. In contrast, the binding affinity of T49Delta to adrenodoxin reductase and cytochrome P-450 11A1 (CYP11A1) is dramatically reduced. These results led to the conclusion that Thr-49 modulates the redox potential in adrenodoxin and that the cluster-binding loop around Thr-49 represents a new interaction region with the redox partners adrenodoxin reductase and CYP11A1. In addition, variations of the apparent rate constants of all mutants for CYP11A1 reduction indicate the participation of residue 49 in the electron transfer pathway between adrenodoxin and CYP11A1.

[New implications for mental disorders treatment: pharmacogenetic studies of dopaminergic and serotonergic neurotransmission systems]. / Nowe perspektywy w leczeniu chorób psychicznych--badania farmakogenetyczne ukladów neuroprzekaznictwa dopaminergicznego i serotoninergicznego.

The aim of this article is to summarize the present state of pharmacogenetical knowledge compiled and based on various publications in this matter. Thanks to developing cloning and DNA-analysis techniques it is possible to analyze numerous proteins synthetized in the central nervous system. Several polymorphism sites in coding genes have already been located--first of all for some genes coding receptors linked to protein G, especially for dopamine and serotonine receptors. Some of mutations may influence the primary structure of receptor protein and in that way be responsible for alteration of receptors functioning. This is likely to be the reason for the difference in reaction to drugs in many patients. A couple of trials dealing with patient's response to neuroleptics in correlation with receptor genes polymorphism have already been completed. The results are promising. The assumption that inventing new drugs should be correlated with collecting DNA samples from patients to evaluate further pharmacogenetical linkage seems to be essential.

The role of microcirculatory techniques in patients with diabetic foot syndrome.

BACKGROUND: Diabetic foot syndrome (DFS) is a frequent complication of long-standing diabetes mellitus, occurring in 10 to 30 percent of all diabetics with a vital risk for the affected limb and high mortality rates. Macroangiopathy, diabetic polyneuropathy and infections are trigger factors for DFS. Recent results imply a pathogenic role of functional and structural microcirculatory changes. The exact role of microangiopathy and the value of microcirculatory diagnostic methods in DFS have not yet been defined. PATIENTS AND METHODS: 78 patients with DFS (28 type I, 50 type II diabetics, mean age 63 years) were evaluated with video capillary microscopy, transcutaneous partial oxygen tension (tcpO2) measurement and laser Doppler fluxmetry (LDF) at the forefoot of the affected leg at admission and after revascularisation. Mean hospital stay was 28 +/- 11.7 days. Patients were stratified according to the etiology of DFS in patients with neuropathic lesions, macroangiopathic ulcers and mixed neuropathic-angiopathic lesions. RESULTS: All groups had impaired microcirculation, and significant differences between groups were found in respect to capillary density. Reactive hyperemia, LDF pattern and tcpO2 did not differ significantly. Microcirculatory examinations did not yield additional information to clinical and Doppler sonographic results. CONCLUSION: In clinical practice, the role of microcirculation evaluation techniques for diabetic foot syndrome is limited.

Vertebrate-type and plant-type ferredoxins: crystal structure comparison and electron transfer pathway modelling.

Crystallographic analysis of a fully functional, truncated bovine adrenodoxin, Adx(4-108), has revealed the structure of a vertebrate-type [2Fe-2S] ferredoxin at high resolution. Adrenodoxin is involved in steroid hormone biosythesis in adrenal gland mitochondria by transferring electrons from adrenodoxin reductase to different cytochromes P450. Plant-type [2Fe-2S] ferredoxins interact with photosystem I and a diverse set of reductases.A systematic structural comparison of Adx(4-108) with plant-type ferredoxins which share about 20 % sequence identity yields these results. (1) The ferredoxins of both types are partitioned into a large, strictly conserved core domain bearing the [2Fe-2S] cluster and a smaller interaction domain which is structurally different for both subfamilies. (2) In both types, residues involved in interactions with reductase are located at similar positions on the molecular surface and coupled to the [2Fe-2S] cluster via structurally equivalent hydrogen bonds. (3) The accessibility of the [2Fe-2S] cluster differs between Adx(4-108) and the plant-type ferredoxins where a solvent funnel leads from the surface to the cluster. (4) All ferredoxins are negative monopoles with a clear charge separation into two compartments, and all resulting dipoles but one point into a narrow cone located in between the interaction domain and the [2Fe-2S] cluster, possibly controlling predocking movements during interactions with redox partners. (5) Model calculations suggest that FE1 is the origin of electron transfer pathways to the surface in all analyzed [2Fe-2S] ferredoxins and that additional transfer probability for electrons tunneling from the more buried FE2 to the cysteine residue in position 92 of Adx is present in some.

Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism.

We analyzed a novel functional 30-bp repeat polymorphism in the promoter region of the X-chromosomal monoamine oxidase A gene (MAOA) to test whether length variation of the repeat polymorphism contributes to variation in the individual vulnerability to antisocial behavior and liability to alcohol dependence. The repeat number (3-5) of the MAOA polymorphism was assessed in 488 male subjects of German descent, a sample comprising 185 psychiatrically screened control subjects and 303 alcohol-dependent subjects including 59 alcoholics with antisocial personality disorder. The frequency of the low-activity 3-repeat allele was significantly increased in 59 antisocial alcoholics compared to 185 control subjects (51 vs. 35%; P = 0.031) and to 244 alcoholics without antisocial personality disorder (51 vs. 32%; P = 0.008), respectively. We found no significant difference in the frequency of the 3-repeat allele between 244 alcoholics without an antisocial personality disorder and the control subjects. Our findings suggest that the low-activity 3-repeat allele of the MAOA promoter polymorphism confers increased susceptibility to antisocial behavior rather than alcohol dependence per se in alcohol-dependent males.

Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application.

OBJECTIVE: Despite modern concepts in therapy by low-dose insulin application and better care in intensive care units (ICUs), there still is a mortality of 5-10% for severe diabetic ketoacidosis (DKA). The aim of this study was to develop a therapy concept to reduce complications and mortality in DKA. RESEARCH DESIGN AND METHODS: From 1986 to 1997, 114 consecutive patients (mean [range]; age 34 [11-74] years) with type 1 diabetes suffering from severe DKA were treated on ICUs and investigated in a retrospective and prospective study. The following are the criteria for admission onto ICUs: < 7.20 pH level, > 300 mg/dl blood glucose, less than -12 mmol/l base excess, or < 300 mg/dl blood glucose plus severe symptoms (i.e., coma). We treated patients according to the following concepts: very-low-dose insulin application by a basal insulin infusion of 1 U/h (0.5-4.0 U/h i.v.), maximal decrease of blood glucose level by 50 mg. dl-1. h-1, slow-motion reequilibration by fluid substitution of 1,000 ml/h (Ringer-Lactate, NaCl 0.9% or half-electrolyte fluids) in the first 4 h, potassium replacement and heparin (500-1,000 U/h i.v.). RESULTS: When patients were admitted to ICU, we found the following parameters: mean (range); 609.0 (86.0-1,428.0) mg/dl blood glucose level; 7.13 (6.53-7.36) pH level; and -19.7 (-41.2 to -7.0) mmol/l base excess. After 12 h of treatment, we reached the following parameters: mean values; 251 mg/dl blood glucose level, 7.31 pH level, and -9.37 mmol/l base excess level. All patients survived without any lasting deficiencies or fatal complications. CONCLUSIONS: Very-low-dose insulin application and slow-motion reequilibration plus monitored substitution of electrolytes are the basic strategies in the treatment of severe DKA. In our view, small doses of infused insulin are the main reason for the safe results of this therapy program.

Association analysis of a PAX-6 gene promoter-associated polymorphic repeat with alcohol dependence.

The human paired box-containing gene PAX-6 participates in the development and plasticity of the brain including the limbic system, the neural system that plays a crucial role in reward processes. We have reported recently a polymorphic dinucleotide repeat sequence with the structure (AC)m(AG)n, which is located approximately 1 kb upstream of the transcription initiation site associated with promoter B and confers allelic variation of PAX-6 expression in the human brain. In the present association study we tested whether length variation of PAX-6 gene-linked polymorphic region (PAX-6 LPR) influences susceptibility to alcohol dependence.The repeat length of the PAX-6 LPR was assessed in 354 control subjects and 328 alcohol-dependent patients, including four subgroups with a presumed substantial genetic predisposition: (a) with a history of withdrawal complications (n=100); (b) with a history of parental alcoholism (n=115); (c) with early onset (n=67) and (d) with dissocial personality disorders (n=54). Allelic distribution of the PAX-6 LPR did not differ significantly between the controls and the entire group of alcohol-dependent patients χ²=0.015, df 1, p=0.904), or any of the subgroups of patients with severe alcoholism. Our results do not provide evidence that length variation of the PAX-6 LPR contributes to the pathogenesis of alcohol dependence.

Gene expression and activity of specific opioid-degrading enzymes in different brain regions of the AA and ANA lines of rats.

There is increasing evidence that alcoholism runs in families suggesting that genetic factors may play a role. In support of this hypothesis, the alcohol-preferring (AA) and the alcohol-avoiding (ANA) rat lines have been developed through selective outbreeding. Numerous studies indicate that the endogenous opioid system may be involved in controlling ethanol consumption. Changes in opioid peptides and opioid receptors have been described after ethanol intake. But, the influence of ethanol on peptidolytic degradation of opioid peptides has been largely ignored, although the peptidase-mediated metabolism of neuropeptides is known as an important regulatory site of peptidergic transmission. Neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE) degrade neuropeptides, including enkephalin and are expressed in the brain. Furthermore, a good correspondence between the regional distribution of NEP and opioid receptors in rat brain has already been reported pointing to a possible role of NEP in regulating opioid peptides. For both enzymes studied, the gene expression pattern was found to be in good agreement with the corresponding enzyme activities in the brain regions investigated, showing the highest levels for both specific mRNAs and enzyme activities in the striatum. Differences in both measured parameters were detected in distinct brain regions of AA and ANA rats. Furthermore, in some brain regions discrepancies between ACE and NEP mRNA levels and the corresponding enzyme activities were observed. For example, in olfactory bulb and striatum such discrepancies were found for both enzymes studied. In tegmentum/colliculi a higher NEP gene expression in AA rats was associated with a higher NEP enzyme activity compared to the amounts found in ANA rats.

Receptor-mediated activation of G-proteins by kappa opioid agonists in frog (Rana esculenta) brain membranes.

This study delineates the heterotrimeric guanine nucleotide binding regulatory protein (G-protein) types in frog (Rana esculenta) brain membranes and their activation by kappa opioid agonists. Ethylketocyclazocine (EKC), trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)b enzeneacetamide (U-50,488) and bremazocine displayed dose-dependent, norbinaltorphimine-reversible stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding in crude membrane preparations. G-proteins were identified by Western-blotting using previously characterized specific antisera that were generated against mammalian G-protein alpha-subunits and beta-subunits. A photoreactive guanosine 5'-triphosphate (GTP) analog, [alpha-32P]GTP azidoanilide ([alpha-32P]AA-GTP) irreversibly labeled four proteins in the molecular weight range of 39-43 kDa. Ethylketocyclazocine and U-50,488 stimulated photolabelling of these proteins among which the 39 kDa band comigrated with the protein specifically labelled with the alpha(i2) antibody and the 40 kDa band was identified as alpha(o1). The other two bands were also stained with the alpha(common) antibody, but were not further identified. These results suggest that the endogenously expressed kappa opioid receptors that are present in frog brain interact with multiple G-proteins in situ. Furthermore, the structure of most G-proteins seems to be well preserved during phylogenesis.

Alcohol induces formation of morphine precursors in the striatum of rats.

Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to play a role in the pathogenesis of alcoholism. The present study describes the alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and Norcoclaurine in the rat brain. These compounds are of special interest since both were found as being intermediates in the biosynthesis of morphine in the opium poppy. The concentration of both TIQs were determined in different brain regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas chromatography/mass spectrometry was used for the detection and quantification of the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in the striatum of those rats which had consumed alcohol for 18 month, neither in other brain regions nor in any brain regions of the controls or the short term (6 month) alcohol treated rats. These findings and the fact that those tetrahydroisoquinolines were only detected in the striatum of the alcohol fed rats and were present only as the S-enantiomers suggest that an alcohol induced biosynthetic pathway exists in the mammalian brain.