Radioprotective effects of thiomethylhydantoin derivatives on Escherichia coli and mice

Protection of Escherichia coli NIHJ and C57BL mice from the effects of 60Co gamma-rays provided by S-alk(en)yl-L-cysteines and their hydantoin derivatives was examined. E. coli (10(6) cells/ml) suspended in a 20 mM aqueous solution of one of the drugs was irradiated with 60 Gy of gamma-rays. Five week-old male mice were exposed to 5.0-9.5 Gy of gamma-rays after a single intraperitoneal injection of 0.75 mmol/kg body weight of each compound. In both E. coli and mice, S-allyl compounds afforded more effective radioprotection than S-propyl compounds. The replacement of the alpha-hydrogen of S-substituted cysteines by methyl groups decreased the radioprotective effect. Hydantoin derivatives were much more radioprotective than the original sulfur-containing amino acids. Especially, DL-5-allylthiomethyl-5-methylhydantoin had a remarkable radioprotective effect in mice. The gamma-radiolysis mechanism of thiomethylhydantoin derivatives was discussed in connection with the radioprotective effect of the drugs.     

Spontaneous regression of gastric varices after iatrogenic injury to a gastrorenal shunt

We present a patient with gastric varices complicating portal hypertension caused by liver cirrhosis related to hepatitis C virus. The patient underwent balloon‐occluded retrograde transvenous obliteration. The gastric varices almost completely disappeared, without any sclerotic agent being used, after iatrogenic injury of the gastrorenal shunt at the time of the interventional procedure.     

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

Dynamic aspects of expanding cava septi pellucidi et Vergae

Summary Two paediatric patients with expanding cysts of the cava Vergae et septi pellucidi are presented. In the first patient, consecutive CT scans showed agrowing cavum thought to be responsible for his dramatic increase in head circumference. In the other patient, the expanding cavum was discovered because a routine skull X-ray after minor head trauma revealed marked impressiones digitatae.Both patients were successfully treated with stereotactically placed internal shunts from the cysts via the lateral ventricle to the subarachnoid space. During this procedure, contrast medium was instilled, and the cysts were visualized on postoperative CT scans.Some dynamic aspects of such expanding cava are discussed.     

Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

BACKGROUND--Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS--Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS--Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS--The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.     

Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery: time-dependency and stimulus specificity.

1. By use of front-surface fluorometry with fura-2-loaded rabbit femoral arterial strips, both the cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored. By utilizing the [Ca2+]i-force curves, we were thus able to examine the temporal changes in the relationships between [Ca2+]i and force ([Ca2+]i-force relationship) during contractions induced by a high external K+ solution, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). 2. The 'basic' [Ca2+]i-force relationship of the Ca(2+)-induced contractions was obtained by the cumulative applications of extracellular Ca2+ (0-10 mM) during 118 mM K(+)-depolarization (Ca(2+)-contractions). 3. When each vascular strip was exposed to high external K+ (30 mM K(+)-118 mM K+) solutions, the [Ca2+]i abruptly increased until it reached a peak, and then slightly decreased and eventually reached a steady-state level. The force also rapidly rose to reach a maximum plateau level. The changes in [Ca2+]i were more rapid than those in the force. Thus, the [Ca2+]i-force curves observed during the contractions induced by high+ (30 mM-118 mM) solutions showed a counter-clockwise rotation, over time. The entire curve shifted to the right, in a concentration-dependent manner, as compared with the line of the 'basic' [Ca2+]i-force relationship of the Ca(2+)-contraction. However, the [Ca2+]i-force relationship of the steady-state of contractions induced by the single dose applications of high K+ (30 mM-118 mM) overlapped with the line of the 'basic' [Ca2+]i-force relationship of Ca(2+)-contractions. 4. As references, the levels of [Ca2+]i and the force at rest (without stimulation) and at the steady-state of the contractions induced by a single dose application of 118 mM K+ solution were designated as 0% and 100%, respectively. When the vascular strips were exposed to NA (10(-5) M) and to 5-HT (10(-4) M), the [Ca2+]i abruptly rose, and reached a peak (107.1 +/- 5.8%) and 101.3 +/- 2.8%, respectively) after 1 min and 2 min, respectively (the [Ca2+]i-rising phase), and thereafter declined with a similar time course (the [Ca2+]i-declining phase) until reaching a low steady level (the steady-state phase). The force induced by 10(-5) M NA and 10(-4) M 5-HT reached a peak at 4 min (129%) and at 2 min (115%), respectively, and thereafter gradually declined. In contrast to the similarity in the [Ca2+]i transient between NA and 5-HT, the force induced by NA declined more slowly and reached higher steady levels than that seen with 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)