Effect of illuminated nifedipine, a potent antioxidant, on intestinal and vascular smooth muscles.

1. The effects of nifedipine (Nif) and its illuminated nitroso product nitrosopine (NTP) were investigated on lipid peroxidation, KCl elevated smooth muscle tension, and ionic currents of single smooth muscle cells. 2. Illumination of Nif at 400-700 nm within 24-48 h changed it completely to a potent antioxidant, NTP. 3. Nif relaxed the KCl-induced contractions of guinea-pig taenia caeci and rat aorta and reduced the amplitude of the evoked inward Ca2+ current of taenia caeci cells in a concentration-dependent manner. NTP (up to 100 microM) was ineffective in this respect. Pretreatment by NTP (10 microM) did not affect the actions of Nif. 4. The evidence suggests that NTP, generated by day-light illumination from Nif, exerts antioxidant activity but is devoid of voltage-dependent Ca2+ channel (VDC) blocking property and does not interfere with the action of Nif on the smooth muscle cell membrane VDC.     

Perflubron Emulsion in Prolonged Hemorrhagic Shock: Influence on Hepatocellular Energy Metabolism and Oxygen-dependent Gene Expression

Background: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion.

Methods: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation.

Results: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone.     

Experimental induction of embryo-derived teratomas and teratocarcinomas in mice

The present study deals with the induction of teratomas and teratocarcinomas in two strains of mice (C3H/Bln and 129/terSv). 6 to 7 days old egg cylinders were transplanted beneath the kidney capsule of adult syngeneic male and female recipients. Out of 115 grafted embryos 32 gave rise to teratoid tumors. Both the overall tumor incidence (teratomas and teratocarcinomas) and the overall percentage of teratocarcinomas were approximately the same in the strains used. In strain C3H/Bln the gender of the recipient seemed to influence the outgrowth of malignant tumors. Two transplantable C3H-teratocarcinomas could be established (DTC-4, DTC-8). Up to date both have retained their pluripotent differentiation pattern which makes them useful for intended further investigations.     

Morbidität nach Herztransplantation

The morbidity in the long-term course following heart transplantation in childhood is mainly determined by the morbidity of the transplanted graft, by side effects caused by immunosuppression and by psychosocial morbidity due to the special situation of life and growing up with a transplanted heart. Transplant vasculopathy as a specific disease of the transplanted organ itself, is a common complication following heart transplantation and is an important factor of morbidity and mortality, considerably limiting the long-term prognosis. Progressive disturbance of renal function and cumulative incidence of malignant tumors is a further factor limiting prognosis caused by the side effects of immunosuppression.     

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.