Effect of unilateral ureteral occlusion on fibrin deposition in the kidney and renal blood flow during intravascular coagulation in rat

The effect of unilateral ureteral occlusion on fibrin deposition in the kidney and the interrelation of the fibrin deposition and the renal blood flow was studied in rat. Intravascular coagulation in the kidney was induced by infusion of thrombin and inhibition of fibrinolysis with tranexamic acid. The effects unilateral occlusion of the ureter for 1 and 24 h on fibrin deposition and renal blood flow were studied. Fibrin in the kidneys was quantitated by intravenous injection of 125I-labelled fibrinogen 24 h before the experiment. The renal blood flow was measured before and after infusion of thrombin by injection of 85Sr- and 141Ce-labelled microspheres into the left ventricle. After ureteral occlusion for 1 h the deposition of fibrin in the kidneys was unaffected. After 24 h substantially less fibrin deposition was found in the occluded than in the unoccluded kidney (0.3 +/- 0.2 and 5.7 +/- 1.6 mg, respectively; p less than 0.05). Before thrombin infusion the blood flow to the occluded kidney was less than that in the unoccluded kidney (2.1 +/- 0.8 and 3.7 +/- 1.2 ml/min, 100 g body weight, respectively; p less than 0.05). The blood flow after infusion of thrombin was equally reduced in both kidneys. The results contradict the hypothesis that vasoconstriction increases the amount of fibrin in the kidneys in thrombin-induced intravascular coagulation.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

The influence of different levels of dietary fat on the incidence and growth of MNU-induced mammary carcinoma in rats

This study describes the influence of isocalorically fed diets (containing different amounts of fat) on tumor incidence and parameters of fat metabolism in female Sprague-Dawley rats. Comparisons are made between rats induced with methylnitrosourea (25 mg/kg body wt) and untreated controls (Group I). The animals received either control diets (3.9% fat by weight, Groups I and II) or fat-enriched diets (10.7%, Group III; 15.6%, Group IV; 21.4%, Group V) over a period of 180 days. At the termination of the experiment, intake of the diet containing 10.7% fat by weight (24% fat per total calories) was associated with the highest tumor incidence. Comparing the different diets, liver lipid concentrations in the individual groups increased with increasing dietary fat, whereas the total lipid in plasma decreased. During the feeding period, total lipid of the liver and plasma, and plasma cholesterol, increased in all groups, but triglycerides of plasma decreased. However, when plasma cholesterol and triglycerides were calculated as a relative amount of total lipid in plasma, cholesterol was found to be significantly decreased in Groups III and IV, and triglycerides were increased in Group III but decreased significantly in Groups I, II, and V at the end of the experiment.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

The herbal preparation STW5 (lberogast®) has potent and region-specific effects on gastric motility

Functional dyspepsia (FD) is amongst the most common functional gastrointestinal disorders. Symptomatic treatment includes the use of herbal preparations whose effects on gastric motility are unclear. The present study aimed at investigating the effects of STW 5 (Iberogast), a fixed combination of hydroethanolic herbal extracts, on gastric motility in vitro. Muscle strips from guinea-pig gastric fundus, corpus and antrum were set up in organ baths either in circular or longitudinal orientation. Addition of ethanol-free STW 5 to the organ baths (32-512 microg mL(-1)) dose-dependently evoked a sustained and reversible relaxation of circular and longitudinal fundus and corpus muscle strips without changes in phasic activity. In contrast, antral muscle strips responded to STW 5 with a significant increase in the contractile force of phasic contractions without changes in tone. All effects were resistant to tetrodotoxin (0.5 micromol L(-1)), atropine (1 micromol L(-1)), omega-conotoxin GVIA (0.5 micromol L(-1)), capsaicin (1 micromol L(-1)) or L-NAME (100 micromol L(-1)), suggesting that neither nerves nor nitric oxide pathways were involved. These data demonstrate that STW 5 profoundly alters gastric motility in a region-specific but not layer-specific manner and thus implicates Iberogast in the treatment of FD patients suffering from motility disorders with impaired fundus accommodation and/or antral hypomotility.     

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Die dopplersonographische Bestimmung der maximalen Blutströmungsgeschwindigkeit in der Diagnostik peripherer arterieller Verschlußkrankheiten bei Diabetes mellitus

Summary Seventy-five diabetic and 40 nondiabetic subjects who where suffering from peripheral vascular disease were studied in order to determine whether the degree of the severity of their disease can be better calculated by Doppler ultrasound examinations of the peak velocity than by the systolic pressure of the peripheral bloodstream. In 46 examinations of normal controls the mean value of the peak velocity was 13.3±3.3 cm/s with a standard deviation of 15.4%±13.2% on one day and 16.1%±15.9% on different days. Considering patients with or without diabetes mellitus the velocity was significantly decreased in correlation to an increasing degree of severity of the vascular disease (P<0.001); however, the decrease was lower in diabetic than in nondiabetic subjects (6.9±2.8 vs 4.6±6.2,P<0.05). The systolic pressure hardly decreased, but remained higher in all stages of peripheral vascular disease of diabetics than in the nondiabetic subject (P<0.05 toP<0.005). There was a significant decrease of the systolic pressure only in diabetic subjects with the most advanced degree of the disease, i.e. stage IV (P<0.05).It is concluded from this study that Doppler ultrasound measurements of the peak velocity of the peripheral bloodstream are a useful parameter to calculate the degree of severity of the peripheral vascular disease. In addition, it is concluded than peak velocity is an even better prognostic indicator of peripheral vascular disease than is measurement of the systolic blood pressure at the feet.

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Abkürzungen AVK periphere arterielle Verschlußkrankheit - USDI Ultraschall-Doppler-Index - MSBG maximale Blutströmungsgeschwindigkeit - HFV Herzfrequenzvariation     

Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.