Biomedical subjects
Publications and source records attributed to Z Srebro.
Astrocytes protect neurons against: 1. Glutamate excitotoxicity through exchange of glutamine for glutamate. 2. Reactive oxygen and nitrogen (peroxynitrite) species. 3. Toxins of endo- and exogenous origin e.g. cyanide. Astrocytes and microglia also protect neurons by storing excess iron and by brushing away from the brain tissue damaged cell constituents such as aged mitochondria, peroxidized cytomembranes and nitrated proteins.
L-cysteine desulfuration was examined in tissues of Rana temporaria, in October and January. The activities of 3-mercaptopyruvate sulfurtransferase (MPST), cystathionine gamma-lyase (CST) and rhodanese were primarily concentrated in frog liver and kidney. The values of CST and rhodanese activity, as well as sulfane sulfur compounds levels fell in the range characteristic of rat. For each of the investigated tissues changes noted in the enzymatic activities and in the level of glutathione (GSH), protein-bound cysteine (PbCys) and sulfane sulfur compounds were dependent on the month in which the determination was performed, and on the character of the tissue. In such tissues as the liver or gonads, high GSH levels and high activities of MPST (in the liver) or MPST and rhodanese (in the gonads) seemed to accompany protein biosynthesis during hibernation. PbCys, the level of which was consequently diminished in all tissues in January, compensated the absence of exogenous cysteine. A significantly reduced GSH level in the brain in January seemed to be correlated with decreased requirements of the tissue for this important natural antioxidant at diminished thyroid hormones levels in the serum and minimal oxygen consumption during the hibernation. In the kidney, the possible participation of sulfane sulfur compounds in detoxification processes requires elucidation, similarly as in protection against cellular oxidative stress at extremely low levels of GSH.
A short review of recent literature on oxidative stress in Alzheimer's disease is presented. Own results on the content of reduced glutathione and protein-bound sulfhydryl groups in the blood of Alzheimer's disease patients are reported. In comparison with a group of healthy age-matched controls the Alzheimer's disease patients have a decreased level of reduced glutathione in erythocytes and significantly increased amounts of protein-bound sulfhydryl groups in blood plasma.
Aminoguanidine (AG) an inhibitor of NO-synthase reduces cysteine (Cys), cystine (CC), sulfane sulfur (SS) and glutathione (GSH) in brain stems but practically has no effects on the levels of reactive oxygen species (ROS). In cortex AG decreases to a lower degree the concentration of Cys, CC, GSH but in this brain part significantly decreases ROS levels and increases SS. Under the AG action cystathionase (CST) activity very seriously decreases in stems and in cortex and simultaneously activity of 3-mercaptopyruvate sulfurtransferase (MPST) increases. The morpholinosydnonimine (SIN-1) the specific donor of NO and O2 only slightly reduces Cys and GSH in brain stems and ROS and SS remain at the control levels. Simultaneously, there is an increase in cortex of the amounts of GSH with the reduction of ROS and SS. Furthermore, SIN-1 seriously decreases in stems and cortex the activity of CST and increases the activity of MPST. These results confirmed the relationship between intracellular levels of NO, sulfhydryl groups, ROS, and anaerobic sulfur metabolism.
The level of 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese activity and the level of sulfane sulfur compounds, L-cysteine and non-protein sulfhydryl groups (NPSH) were compared in cortex and brain stem of mouse. The level of cysteine and sulfane sulfur compounds was higher in brain stem; 107% and 217% of the value determined in cortex, respectively. The activity of MPST and rhodanese showed also increased level in brain stem; 114% and 119% of the value determined in cortex, respectively. The level of NPSH in cortex was about 10% higher in comparison to brain stem. It seems that in brain stem metabolism of sulfane sulfur compounds and/or their accumulation may occur in a higher degree than in cortex.
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Tritiated thymidine and Ehrlich ascites tumour cells were injected intrathecally in adult Balb/c mice. Thymidine penetrated easily into the sphenoid bone marrow, where it labelled numerous leukocytes. The microvessel wall constituted a partly penetrable barrier against the infiltration of Ehrlich ascites tumour cells from arachnoid space into the bone marrow. A possible physiological role of the drainage of substances from the brain into the bone marrow is discussed.
The genetic basis of the limited lifespan and apparently programmed number of divisions in normal, diploid cells is discussed. Two different mechanisms may underlie a programmed inhibition of cell divisions before they age and die: 1. A genetic mechanism involving the CpG sequence in promotor regions of genes. Inactive, but gradually activated basic function genes such as ribosomal and energy metabolism genes, when inactive have their CpG promotor sequences methylated. During each cell division a proportion of 5-methyl cytosines will be oxidatively deaminated leading to C to T transitions. After a certain number of divisions all methylated CpG islands will be mutated with consequent loss of viability and cell death. 2. An epigenetic mechanism involving the methylated promotor sequences of silent growth control genes. After a certain number of divisions with incomplete maintenance methylation, the growth control genes will be derepressed with consequent cessation of proliferation, decline of metabolic activity, ageing, and death.
Histological and autoradiographic studies revealed mitotic activity in the subependymal germinal layer in the brains of adult mice. The number of mitoses observed was higher in animals subjected to administration of haematoporphyrin and selenourea.
Cytoplasmic total RNA in neurons of the supraoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus, and arcuate nucleus was determined cytophotometrically following a single intramuscular dose of 4 IU/kg insulin semilente. A significant decrease was observed after 3, 6, and 12 hours. A return towards normal values was evident after 24 hours and was full after 48 hours only in suprachiasmatic nucleus. Other hypothalamic nuclei did not reach the full normal value in the time interval examined, i.e. 48 hours post-injection.
Kainic acid in a dose of 12 micrograms/g given 1 hour before decapitation strongly modifies the content of cytoplasmic RNA, as determined cytophotometrically, in neurons of the supraoptic, paraventricular, and arcuate nuclei of the hypothalamus of adult mice. This stimulatory action of kainic acid was strongest during the night hours when the control animals exhibited the lowest amounts.
The Cytoplasmic RNA content in neurons of the nucleus suprachiasmaticus was determined cytophotometrically in adult mice following injection of kainic acid. A dose of 12 mg/kg b. w. caused a significant increase in the cytoplasmic RNA content at least between 1 and 15 days postinjection.
A single intramuscular injection of kainic acid (12 micrograms/g body weight, dissolved in 0.1 ml of aqua pro injectione) was administered to adult, sexually mature, male mice. Control mice received equivalent amounts of aqua pro injectione only. Experimental animals were killed 24, 72, 120, and 192 h after the injection, and those of the control group simultaneously with the final experimental one. As determined cytophotometrically, in all the experimental groups a significant increase in the cytoplasmic RNA content of nucleus arcuatus neurons took place, this increase being highest 72 h after kainic acid treatment.
Sexually mature male and female frogs, Rana temporaria L., taken from their natural habitat at the end of the hibernation period, were subjected to treatment with ultrasound of various duration. The ultrasound (frequency, 24 kHz, intensity 0.35 W/cm2) was applied over the whole body in a suitable water bath. Neurons of the nucleus infundibularis dorsalis, medulla oblongata, and the subfornical organ were studied. A considerable increase in the amount of autofluorescent lipofuscin pigment was observed in nerve cells of various regions of the brain of the treated animals. The largest amounts of the lipofuscin pigment were found in those treated for one hour and killed on the fourteenth day following sonication.
An analgesic activity of gamma-butyrolactone was observed and described referring to a facilitated pain killing of certain diseases.
Three days following bilateral adrenalectomy the following findings were revealed in the hypothalamus-hypophysis and circum-ventricular organs of Balb mice: considerable enlargement of neuronal perikarya and nuclei in the nucleus arcuatus of the hypothalamus. Amitotic divisions were frequent in neurons and glial cells. Mitoses were also sporadically encountered. The pars distalis of the hypophysis showed typical post-adrenalectomy changes. In addition, enlargement of the so-called pars rostralis was observed. This part and the pars intermedia showed signs of enhanced secretion. The subfornical organ of the adrenalectomized animals was much smaller than in the controls. The subcommissural organ and pineal gland, on the contrary, were large and apparently actively secreting.
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