Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.     

Breast-sparing therapy of breast cancer: on the combination of radiation therapy with adjuvant chemotherapy

From January, 1975 through June, 1986, 426 patients with mammary carcinomas were submitted to primary, breast-preserving therapy at the Gynecological Hospital of the University of Heidelberg. 212 women with a minimum observation time of twelve months fulfilled the criteria of a "typical" treatment: tumor size up to 3 cm, segment/quadrant resection and axillary lymphonodectomy with at least eight lymph nodes removed, radiotherapy of the residual breast with greater than or equal to 45 Gy, in case of histological lymph node manifestation adjuvant hormonal and/or chemotherapy. The average observation time was 38 months, the medium age 48 years. Patients with histological lymph node manifestations were compared with a matched control group of women treated treated by modified radical therapy. According to the error estimation of Kaplan and Meier (1958), no differences were found for local recurrence rate, disease-free survival, and overall survival. Patients treated by organ-preserving therapy with adjuvant chemotherapy were opposed to a matched control group of women treated only by surgical/radiological, organ-preserving therapy. In patients with chemotherapy, the incidence of cutaneous erythema (29% versus 24%), telangiectasia (34% versus 24%), hyperpigmentation (41% versus 34%) showed an upward tendency, but was not significantly increased. There was no difference in the incidence of clinically palpable fibroses (37% versus 42%) and fibroses shown by mammography (54% versus 51%). The frequency of pneumonitis/fibrosis of the retromammary lung area (22% versus 10%) after chemotherapy was two times higher than in the matched control group not treated by chemotherapy.     

TLC and HPLC Analysis of Alkamides in Echinacea Drugs1,2

HPLC and TLC methods are presented for the analysis of the alkamides in ECHINACEA PURPUREA, E. ANGUSTIFOLIA, and E. PALLIDA. The roots of E. PURPUREA and E. ANGUSTIFOLIA contain different structural types of alkamides, while the roots of E. PALLIDA were almost void of amides. In contrast, the aerial parts of the three ECHINACEA species yielded very similar alkamide patterns. The methods are suitable for the analytical characterization and standardization of the three species.     

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia

The brain serotonin-2A receptor (5-HT_2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT_2AR status before the onset of schizophrenia and before the exposure to antipsychotics. We used [¹⁸F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT_2AR binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT_2AR availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.     

Construction and characterization of Listeria monocytogenes mutants with in-frame deletions in the response regulator genes identified in the genome sequence

Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.     

Schedule and quinine induced deprivation in feeding and refeeding

Twenty female albino rats were adapted to either 0 or 23 hr of food deprivation. Half of each group was then fed 0.125% quinine sulfate adulterated diet for seven days. Following the quinine feeding, ad lib feeding (refeeding) was instituted for 14 days. Several conclusions were drawn from the results: (1) rats on a deprivation schedule fail to show a predicted change to regulation on the basis of taste rather than calories; (2) rats on food deprivation actually increase their relative intake of water; (3) refeeding after a deprivation schedule does not lead to depression of initial intake below normal, but otherwise the process of recovery follows the same course as after total starvation.     

The osmotic behaviour of toad skin epithelium (Bufo viridis)

The effect of saline adaptation on the intracellular Na, K, Cl, P concentrations and dry weight content of the toad skin epithelium (Bufo viridis) was studied using the technique of electron microprobe analysis. The measurements were performed on isolated abdominal skins either directly after dissection or after additional incubation in Ussing-type chambers.Adaptations of the toads to increasing NaCl concentrations for 7 days resulted in increased blood plasma osmolarity and a parallel increase in the cellular electrolyte, P and dry weight concentrations of the epithelium, the K increase representing the most significant fraction of the intracellular osmolarity increase. No evidence was obtained to show that the nucleus and cytoplasm reacted differently from each other and all living epithelial cell types basically showed the same response.Incubation of the isolated skins under control conditions showed a drastic inhibition of the transepithelial Na transport after adaptation to high salinities. In spite of the large variations in the transport rate almost identical intracellular electrolyte concentrations were observed. In tap water adapted toads the average cellular concentrations were 8.8 mmole/kg wet weight for Na, 109.6 for K, 41.5 for Cl, and 135.3 for P, respectively. Incubation of the skin with Ringer's solution of different osmolarities demonstrated that the epithelial cells are in osmotic equilibrium with the inner bathing solution. The results are consistent with the view that the osmotic adaptation is mainly accomplished by the movement of water.This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Stiftung Volkswagenwerk