Time function of corticosteroid levels in the blood plasma of rats under the influence of 222Rn inhalation.

The time function of cortocosteroid level in plasma of rats under two different 222Rn concentrations was investigated. Both curves show a maximum after 8h. Whereas the higher activity of 222Rn produces a second maximum after 5 days, the lower activity reaches its second maximum not before 9 days. From both time functions, a two-step mechanism in the intracellular control can be concluded.     

Protein anabolism in endometrium and myometrium during the growth of induced deciduoma in rats

Summary Protein anabolism in the endometrium and myometrium was studied during the growth of induced deciduoma in terms of incorporation of [¹⁴C]-leucine into proteins. The data show that the specific activity of the proteins was highest 2 days after decidualisation. Protein synthesis in the endometrium studied on that day as a function of time after injection of the labelled amino acid showed a steady increase during the first 2 h. Cycloheximide (2 mg/kg b.wt) administration produced nearly 95% inhibition of protein synthesis in endometrium as well as in myometrium.     

Irradiation of the head by60Co opens the blood-brain barrier for drugs in rats

Summary The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a⁶⁰Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of³H₂O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Leydig cell andΔ 5-3β-hydroxysteroid dehydrogenase activity in the testis of toad (Bufo melanostictus) following cold exposuredehydrogenase activity in the testis of toad (Bufo melanostictus) following cold exposure

Summary Leydig cell nuclear area and ⁵-3-hydroxysteroid dehydrogenase activity were increased in the testis ofBufo melanostictus 2 days after a single short-term cold exposure. Both parameters returned to normal values 4 days later.     

Further evidence for the dissociation of digoxin-like immunoreactivity from Na+, K+-ATPase inhibitory activity

Summary The effects of adrenalectomy or nephrectomy, carried out one hour previously, on the levels of endogenous digitalis-like factors were determined in rat plasma. Factors were assayed by digoxin-like immunoreactivity and direct Na⁺, K⁺-ATPase inhibitory activity. Digoxin-like immunoreactivity significantly decreased one hour after bilateral ablation of adrenals, while Na⁺, K⁺-ATPase inhibitory activity remained unaltered. There were no changes in either activity one hour after bilateral nephrectomy. These results suggest that digoxin-like immunoreactivity may be derived from the adrenal gland or under adrenal control and the major substances detected by digoxin-like immunoreactivity and direct Na⁺, K⁺-ATPase inhibitory activity may be different.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport

Summary Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca⁺⁺-ATPase activity and Ca⁺⁺-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg⁺⁺-, Ca⁺⁺- and (Na⁺+K⁺)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca⁺⁺-ATPase activity, is not related to Ca⁺⁺-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Radiostrontium-Ausscheidung im Kot junger Ratten nach calciumreicher Ernährung

Summary Young immature rats of both sexes were fed with a diet either high (1.95%) or low (0.31%) in Ca content. A s.c. injection of weightless⁹⁰Sr results in a better excretion of radiostrontium with the faeces during feeding with high Ca diet. The retention of activity in the femori 30 days after injection is, in the same case, lower than by feeding with low Ca diet.     

Der Einfluss von Acetylcholin auf die42Kalium-Abgabe postnataler,denervierter und reinnervierter Skeletmuskulatur

Summary The loss of⁴²K from the isolated rat diaphragm into the bathing solution is increased by acetylcholine, (a) 3 to 4 days after birth, (b) 7 to 14 days after sectioning of the phrenic nerve. The⁴²K loss is not altered by acetylcholine in the diaphragm of adult rats and after the denervated diaphragm has become reinnervated.     

Acetylcholinesterase activity in anAedes aegypti cell line

Summary Considerable acetylcholinesterase (AChE) activity was detected in anAedes aegypti established cell line. The enzyme is blocked by 10^–6 M eserine sulfate, displays excess substrate inhibition and slowly hydrolyzes butyrylthiocholine. A 2-fold stimulation of AChE activity was shown after 2 days exposure to 3×10^–7 M -ecdysone. AChE activity found in the fresh medium is the contribution of the fetal calf serum portion. A direct relationship between levels of serum and the AChE activity in the cultured cells was demonstrated.Acknowledgment. I wish to thank Dr J. Peleg of the Israel Institute for Biological Research for providing the starting culture ofAedes aegypti cells.     

Bactericidal activity againstPseudomonas aeruginosa is acquired by cultured human monocyte-derived macrophages after uptake of myeloperoxidase

Myeloperoxidase (MPO) is an enzyme located within polymorphonuclear neutrophils capable of producting cytotoxic oxidant species that are particularly active against bacteria with polysaccharide capsules.Pseudomonas aeruginosa (10⁶ bacteria per 1 ml) are killed within 1 h in vitro by a MPO/H₂O₂/Cl^– system (48 mU=132 ng of MPO). The question arose as to whether human macrophages would acquire cytotoxic activity when loaded with this enzyme. Monocytes were therefore isolated from human blood and cultured for up to ten days to induce maturation to macrophages. These cells lost endogenous MPO within five days while H₂O₂ production in response to stimulation by phorbol myristate acetate (10^–6M) decreased to 23% within ten days. On the other hand, their capacity to take up exogenous MPO increased fourfold from day three to day ten. Human macrophages cultured from eight days (when both H₂O₂ production and MPO uptake were sufficient) were therefore used to study the effects of MPO uptake on cytocidal activity againstPseudomonas aeruginosa. After a 1 h MPO loading period, macrophages (5×10⁵ cells per ml) were incubated in the presence of bacteria (0.5 to 2×10⁶ bacteria per ml) for 2 h at 37°C. At a bacteria/macrophage ratio of 1, only 34.8±7.0% of bacteria survived (compared to killing by non-loaded macrophages), while 74.4±9.3% survived at a ratio of 4. From these results, we conclude that loading macrophages with exogenous MPO could enhance their microbicidal activity, suggesting a potentially useful therapeutic application.     

The effect of chronic heat stress on cortisol levels in the antarctic fishPagothenia borchgrevinki

Radioimmunoassay was used to determine levels of the stress-inducible glucocorticoid, cortisol, circulating in the plasma of the extremely stenothermal Antarctic fishPagothenia borchgrevinki at rest and after heat stress. Fish sampled immediately after capture (–1.9°C) had low cortisol levels (10.4±1.4 ng ml^–1, mean±SEM) as did fish which were laboratory rested for 3 days. Sudden exposure to 5°C (48h) resulted in a peak cortisol value after 3 h (69.9±6.8 ng ml^–1) whereas exposure to 8°C (6h) resulted in a peak value after 1 h (73.5±8.0 ng ml^–1). At both temperatures levels remained significantly elevated (p<0.05) for the entire period of exposure. Increased temperature also resulted in a significant change in haemoglobin, haematocrit and mean cell haemoglobin concentration (MCHC) (p<0.05). Plasma lactate was significantly elevated only after exposure to 8°C (p<0.05). Plasma cortisol levels fromP. borchgrevinki are reported here for the first time and show this cryopelagic Antarctic species to have an unusual hormonal stress profile.     

Effetto della ouabaina sul tessuto nervoso in coltura in vitro

Summary The addition of 1 · 10^–4 ouabain (strophantin-G), a Na⁺-K⁺-dependent ATP-ase inhibitor, to the cultivating medium of chick embryo spinal ganglia in vitro cultures caused the vacuolization of the cytoplasm of the fibroblast-like cells, but not of the nervous ones, after 6 h of culture, with a maximum after 24 h.     

Zeitbedarf der Längsteilung von miteinander verzwirnten Fadenmolekülen

Summary The time requirement is treated for a longitudinal fission by Brownian movement of a very long particle consisting of two or more filaments twisted a great number of times round each other to form a double spiral. It is shown that a comparatively swift disintegration is obtained by partial rotation or torsion round the axis of the spiral, resulting in a loosing of the spiral structure and subsequent separation of the constituents by translational Brownian movement. The time required to separate a double spiral consisting of about 900 turns of a height of 3.4 × 10⁻⁷ cm and a radius of 10⁻⁷ cm, thus having a length of 3 × 10⁻⁴ cm being realized approximately by deoxyribonucleic acid is found by this mechanism to be about 50 to 80 s. The time required to undo the same spiral by unwrapping it turn by turn would be about 150 days. The result of the considerations is related to observations published byAlexander andSteacy on deoxyribonucleic acid. An additional remark stresses the importance of stereochemical asymmetry for the practicability of the mechanism and therefore the importance of optical activity for the time requirement of such disintegrations or transformations of high polymer material occurring in living organisms.      

Effect of insulin in vivo on the synthesis of free fatty acids (FFA) in chicken heart and skeletal muscle

Summary The effect of insulin on the synthesis of free fatty acids from glucose in the skeletal and heart muscles of chicken is examined. 10 min after glucose-(U-¹⁴C) administration, labeled free fatty acids (FFA) appeared in both skeletal and heart muscles. 0.75 IU of insulin kg^–1 b. wt significantly increased the labeled FFA at the 30, 60 and 120 min intervals, with a maximum at 60 min.     

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5^KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5^KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5^KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5^KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5^KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Stimulation of the incorporation of3H-leucine into proteins by oestradiol in the foetal uterus of the guinea-pig

Summary Oestradiol treatment increases the incorporation of³H-leucine into acid insoluble proteins in the foetal guineapig uterus (50–65 days of gestation) 10 times above control values by 8 h and 20 times by 24 h after administration of oestradiol to the mother.     

Differences in membrane ion transport between hepatocytes from the periportal and the pericentral areas of the liver lobule

We studied the Na⁺/K⁺ pump, Na⁺/K⁺ ATPase activity, and oxygen consumption (QO₂) in hepatocytes isolated from the periportal (PH) and pericentral (CH) regions of the liver lobule, to provide an insight into the functional properties of these cells. Na⁺/K⁺ pump activity was determined using⁸⁶Rb⁺ (a functional analog of K⁺) and ouabain, a specific inhibitor of this transport system. Our results indicate the the Na⁺/K⁺, pump and Na⁺/K⁺ ATPase activity are significantly lower in CH than in PH, although basal ouabain-sensitive (OS) QO₂ was negligible in both of these cell preparations. However, OSQO₂ was significantly lower in CH than in PH when the Na⁺/K⁺ pump was activated using the ionophore nystatin in a Na⁺-containing medium. These results indicate that the differences in membrane ion transport exist between hepatocytes from different locations of the liver lobule.     

Effect of various stressors on the levels of lipid peroxide,antioxidants and Na+, K+-ATPase actrivity in rat brain

The level of malondialdehyde (MDA), an index of lipid peroxidation, and the antioxidants superoxide dismutase (SOD) and glutathione (GSH), as well as the activity of Na⁺, K⁺-ATPase, were assessed in whole rat brain after immobilization, anemic hypoxia (NaNO₂) and 72 h starvation. The effect of these stressors on plasma glucose and corticosterone levels was also observed. Hypoxia and starvation stimulated the lipidj peroxide formation in braini as indicated by an increase in the level of MDA, being higher after starvation than hypoxia. Brain SOD activity was also increased in response to hypoxia and starvation while GSH content was only diminished ini hypoxia. However, neither MDA nor antioxidants were affected by immobilization. On the other hand, the activity of brain Na⁺, K⁺-ATPase was significantly increased by immobilization and hypoxia but decreased in starvation. A similar pattern of change was also observed in plasma glucose and corticosterone levels in response to these stressors. These results elucidate differences in the biochemical response of animals towards various types of stress, with increased lipid peroxide formation in hypoxia and starvation.