A gamma-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been recently cloned in the rat and human brain and two variants generated by alternative RNA splicing were identified. In the ...present study, we addressed the question as to whether these variants contribute to the diversity of GABA(B) receptor-mediated physiological responses and constitute real receptor subtypes with distinct functions. To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of (3)HCGP54626-labeled binding GABA(B)R1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABA(B)R1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented.
Background. Fat affects gastric emptying (GE). 5-Hydroxythryptophan (5-HTP) is involved in central and peripheral satiety mechanisms. Influence of 5-HTP in addition to saturated or monounsaturated ...fatty acids (FA) on GE and hormone release was investigated. Subjects/Methods. 24 healthy individuals (12f : 12m, 22–29 years, BMI 19–25.7 kg/m²) were tested on 4 days with either 5-HTP + short-chain saturated FA (butter), placebo + butter, 5-HTP + monounsaturated FA (olive oil), or placebo + olive oil in double-blinded randomized order. Two hours after FA/5-HTP or placebo intake, a 13C octanoid acid test was conducted. Cortisol, serotonin, cholecystokinin (CCK), and ghrelin were measured, as were mood and GE. Results. GE was delayed with butter and was normal with olive ( P < 0.05 ) but not affected by 5-HTP. 5-HTP supplementation did not affect serotonin levels. Food intake increased plasma CCK ( F = 6.136 ; P < 0.05 ) irrespective of the FA. Ghrelin levels significantly decreased with oil/5-HTP ( F = 9.166 ; P < 0.001 ). The diurnal cortisol profile was unaffected by FA or 5-HTP, as were ratings of mood, hunger, and stool urgency. Conclusion. Diverse FAs have different effects on GE and secretion of orexigenic and anorexigenic hormones. Supplementation of 5-HTP had no effect on plasma serotonin and central functions. Further studies are needed to explain the complex interplay.
Women with highly penetrant BRCA mutations have a 55-60% lifetime risk for breast cancer and a 16-59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating that ...environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers.
Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of ≥18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires.
This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE).
ClinicalTrials.gov, NCT02087592.
Abstract Antimicrobial drug resistance in Neisseria gonorrhoeae has become an increasing public health problem. Hence, surveillance of resistance development is of crucial importance to implement ...adequate treatment guidelines. Data on the spread of antibiotic resistance among gonococcal isolates in Germany, however, is scarce. In a resistance surveillance study conducted by the Paul Ehrlich Society for Chemotherapy between October 2010 and December 2011, 23 laboratories all over Germany were requested to send N. gonorrhoeae isolates to the study laboratory in Frankfurt am Main. Species verification was performed biochemically using ApiNH and with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Etest method. For molecular epidemiological analysis, N. gonorrhoeae strains were genotyped by means of N. gonorrhoeae multi-antigen sequence typing. A total of 213 consecutive gonococcal isolates were analyzed in this nationwide study. Applying EUCAST breakpoints, high resistance rates were found for ciprofloxacin (74%) and tetracycline (41%). Penicillin non-susceptibility was detected in 80% of isolates. The rate of azithromycin resistance was 6%, while all strains were susceptible to spectinomycin, cefixime, and ceftriaxone. Molecular typing of gonococcal isolates revealed a great heterogeneity of 99 different sequence types (ST), but ST1407 predominated ( n = 39). This is the first comprehensive German multi-centre surveillance study on antibiotic susceptibility and molecular epidemiology of N. gonorrhoeae with implications for antibiotic choice for treatment of gonorrhoea. The World Health Organization supports the concept that an efficacious treatment of gonorrhoea results in at least 95% of infections being cured. Accordingly, as spectinomycin is not available on the German market, only the third generation cephalosporins cefixime and ceftriaxone are regarded as valuable drugs for empirical treatment of gonorrhoea in Germany.
A three-plasmid yeast expression system utilizing the portable small ubiquitin-like modifier (SUMO) vector set combined with the efficient endogenous yeast protease Ulp1 was developed for production ...of large amounts of soluble functional protein in
Saccharomyces cerevisiae. Each vector has a different selectable marker (URA, TRP, or LEU), and the system provides high expression levels of three different proteins simultaneously. This system was integrated into the protocols on a fully automated plasmid-based robotic platform to screen engineered strains of
S. cerevisiae for improved growth on xylose. First, a novel PCR assembly strategy was used to clone a xylose isomerase (XI) gene into the URA-selectable SUMO vector and the plasmid was placed into the
S. cerevisiae INVSc1 strain to give the strain designated INVSc1-XI. Second, amino acid scanning mutagenesis was used to generate a library of mutagenized genes encoding the bioinsecticidal peptide lycotoxin-1 (Lyt-1) and the library was cloned into the TRP-selectable SUMO vector and placed into INVSc1-XI to give the strain designated INVSc1-XI-Lyt-1. Third, the
Yersinia pestis xylulokinase gene was cloned into the LEU-selectable SUMO vector and placed into the INVSc1-XI-Lyt-1 yeast. Yeast strains expressing XI and xylulokinase with or without Lyt-1 showed improved growth on xylose compared to INVSc1-XI yeast.
Mental disorders in primary care Herzig, Lilli; Mühlemann, Nicole; Bischoff, Thomas
Revue médicale suisse,
2010-May-19, Letnik:
6, Številka:
249
Journal Article
Recenzirano
Mental disorders (depression, anxiety and somatization) are frequent in Primary care and are often associated to physical complaints and to psychosocial stressors. Mental disorders have in this way a ...specific presentation and in addition patients may present different associations of them. Sometimes it is difficult to recognize them, but it is important to do so and to take rapidly care of these patients. Specific screening questions exist and have been used in a research of the Institute of General Medicine and the Department of Ambulatory Care and Community Medicine (PMU), University of Lausanne, Switzerland.
Seasonality research: the state of the art Koenig-Lewis, Nicole; Bischoff, Eberhard E.
The international journal of tourism research,
07/2005, Letnik:
7, Številka:
4-5
Journal Article
In cases of rare cancer entities, such as malignant melanoma of the conjunctiva, there are often no evidence-based national guidelines available. Standard operating procedures (SOP) are an ...alternative in these cases.
The aim of this project was to develop a consensus SOP for diagnosis, treatment, and follow-up care of conjunctival melanomas between the 14 Centers of Excellence in Germany supported by German Cancer Aid.
The SOP was prepared according to a defined process including timelines, flow of information, and roles.
This is the first consensus SOP of the Centers of Excellence in Germany (certified by the German Cancer Aid) regarding diagnosis, treatment, and follow-up for malignant melanomas of the conjunctiva.