EFFECTS OF X-RADIATION AND OF METABOLIC INHIBITORS ON RAT THYMOCYTES IN VITRO

1962 ◽  
Vol 40 (11) ◽  
pp. 1535-1552 ◽  
Author(s):  
D. K. Myers ◽  
Donna E. DeWolfe ◽  
Kimiko Araki
Keyword(s):  
Oxygen Consumption ◽  
Normal Cell ◽  
Cell Metabolism ◽  
Metabolic Inhibitors ◽  
Low Doses ◽  
Ph Values ◽  
Atp Levels ◽  
Different Temperatures ◽  
High Doses

The survival of X-irradiated thymocytes in vitro was studied after incubation for various periods of time and at different pH values as well as at different temperatures. Death at 25 °C following exposure to high doses of X-radiation may be due to the liberation of destructive enzymes. The effects of high doses could be largely prevented by addition of nicotinamide after irradiation.The cause of cell death at 37 °C following exposure to low doses of X-radiation is still uncertain. Some metabolic inhibitors also showed a considerable difference in their toxicity to thymocytes at 37 °C and at 25 °C. Dinitrophenol, for example, was highly toxic at 37 °C but almost ineffective in killing cells at 25 °C, even though it produced similar decreases in ATP levels at both temperatures. The marked difference in survival of irradiated thymocytes at 37 °C and at 25 °C could therefore be explained if low doses of X-radiation interfered with the normal cell metabolism. However, low doses of radiation, unlike dinitrophenol, did not produce any immediate decrease either in ATP levels or in oxygen consumption of thymocyte suspensions.

EFFECTS OF X-RADIATION AND OF METABOLIC INHIBITORS ON RAT THYMOCYTES IN VITRO

1962 ◽  
Vol 40 (1) ◽  
pp. 1535-1552 ◽  
Author(s):  
D. K. Myers ◽  
Donna E. DeWolfe ◽  
Kimiko Araki
Keyword(s):  
Oxygen Consumption ◽  
Normal Cell ◽  
Cell Metabolism ◽  
Metabolic Inhibitors ◽  
Low Doses ◽  
Ph Values ◽  
Atp Levels ◽  
Different Temperatures ◽  
High Doses

The survival of X-irradiated thymocytes in vitro was studied after incubation for various periods of time and at different pH values as well as at different temperatures. Death at 25 °C following exposure to high doses of X-radiation may be due to the liberation of destructive enzymes. The effects of high doses could be largely prevented by addition of nicotinamide after irradiation.The cause of cell death at 37 °C following exposure to low doses of X-radiation is still uncertain. Some metabolic inhibitors also showed a considerable difference in their toxicity to thymocytes at 37 °C and at 25 °C. Dinitrophenol, for example, was highly toxic at 37 °C but almost ineffective in killing cells at 25 °C, even though it produced similar decreases in ATP levels at both temperatures. The marked difference in survival of irradiated thymocytes at 37 °C and at 25 °C could therefore be explained if low doses of X-radiation interfered with the normal cell metabolism. However, low doses of radiation, unlike dinitrophenol, did not produce any immediate decrease either in ATP levels or in oxygen consumption of thymocyte suspensions.

scholarly journals Hormetic effect of amyloid-beta peptide in hippocampal synaptic plasticity and memory

2021 ◽  
Vol 11 (40) ◽  
pp. 156-156
Author(s):  
Daniela Puzzo ◽  
Agostino Palmeri
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Beta ◽  
Hippocampal Slices ◽  
Reference Memory ◽  
High Dose ◽  
Low Doses ◽  
Hormetic Effect ◽  
Physiologic Function ◽  
High Doses

Background: The term hormesis refers to a biphasic dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition represented by a J-shaped or U-shaped curve, depending on the parameter measured (Calabrese and Baldwin, Hum Exp Toxicol, 2002). Indeed, several, if not all, physiological molecules (i.e. glutamate, glucocorticoids, nitric oxide) are likely to present a hormetic effect, exhibiting opposite effects at high or low concentrations. In the last few years, we have focused on amyloid-beta (A), a peptide widely known because it is produced in high amounts during Alzheimer’s disease (AD). A is considered a toxic fragment causing synaptic dysfunction and memory impairment (Selkoe, Science, 2002). However, the peptide is normally produced in the healthy brain and growing evidences indicate that it might have a physiologic function. Aim: Based on previous results showing that picomolar concentrations of A42 enhance synaptic plasticity and memory (Puzzo et al, J Neurosci, 2008) and that endogenous A is necessary for synaptic plasticity and memory (Puzzo et al, Ann Neurol, 2011), the aim of our study was to demonstrate the hormetic role of A in synaptic plasticity and memory. Methods: We used 3-month old wild type mice to analyze how synaptic plasticity, measured on hippocampal slices in vitro, and spatial reference memory were modified by treatment with different doses of A (from 2 pM to 20 μM). Results: We demonstrated that A has a hormetic effect (Puzzo et al, Neurobiol Aging, 2012) with low-doses (200 pM) stimulating synaptic plasticity and memory and high-doses (≥ 200 nM) inhibiting these processes. Conclusions: Our results suggest that, paradoxically, very low doses of A might serve to enhance memory at appropriate concentrations and conditions. These findings raise several issues when designing effective and safe approaches to AD therapy.

FACTORS AFFECTING THE INCORPORATION OF RADIOACTIVE PHOSPHATE INTO THE PHOSPHOLIPIDS OF SLICES OF CAT BRAIN

1954 ◽  
Vol 32 (1) ◽  
pp. 50-59 ◽  
Author(s):  
K. P. Strickland
Keyword(s):  
Oxygen Consumption ◽  
Inorganic Phosphate ◽  
Brain Slices ◽  
Phospholipid Fraction ◽  
Metabolic Inhibitors ◽  
Factors Affecting ◽  
Wide Range ◽  
Cat Brain

Slices of cat brain respiring in a Krebs–Ringer bicarbonate medium were found to incorporate radioactive inorganic phosphate (P32) into the phospholipid fraction. The addition of glucose or mannose increased the incorporation of P32 into the phospholipids. Fructose caused a small increase, whereas galactose was without effect. Pyruvate and lactate increased the incorporation of P32 into the phospholipids. Succinate, L (+)-glutamate, D (−)-glutamate, α keto-glutarate, citrate, and L-malate failed to support the incorporation.Anaerobic conditions and homogenization of the tissue prevented the in vitro incorporation of P32 into the phospholipids of cat brain. A wide range of metabolic inhibitors (cyanide, azide, malononitrile, chloretone, nembutal, iodoacetate, and fluoride), in concentrations that inhibit the oxygen consumption of brain slices, inhibited the incorporation. The incorporation was also inhibited by 2,4-dinitrophenol in concentrations that do not decrease the oxygen consumption of brain slices.These findings indicated that the incorporation of P32 into the phospholipids of slices of cat brain is a metabolic phenomenon and is dependent upon the maintenance of an adequate phosphorylating mechanism within the slice.

Effets de rayons γ 60Co sur des vitroplants haploïdes et diploïdes de Gerbera jamesonii

1987 ◽  
Vol 65 (10) ◽  
pp. 2074-2083 ◽  
Author(s):  
M.-A. Dubuc-Lebreux ◽  
J. Vieth
Keyword(s):  
Optimal Dosage ◽  
Anthocyanin Content ◽  
Low Doses ◽  
Gerbera Jamesonii ◽  
Plantlet Production ◽  
Overall Evaluation ◽  
Total Growth ◽  
Γ Rays ◽  
High Doses

Gerbera jamesonii ‘Super Gerbera’ explants were irradiated in vitro with 60Co γ-rays (8–100 Gy). Some received a single dose, while others received two or three at successive multiplication cycles. Several parameters were measured after 6 weeks of in vitro culture, to compare the effects of irradiation on haploid and diploid clones. Productivity is linked to the ploidy level, whereas total growth is not. Total growth inhibition is proportionate to the given dose. Callus and plantlet growth are either inhibited or stimulated, depending on the type of treatment. Callus growth is stimulated by low doses, which induce the transformation of apices into calli; treatment of successive cycles with low doses (20 and 30 Gy for diploids, 10 and 15 Gy for haploids) ensures better plantlet development. High doses inhibited growth of calli and plantlets up to the 50% level. Variations in morphology and in chlorophyll and anthocyanin content were observed among haploid and diploid irradiated explants. Plantlet production is a good criterion for an overall evaluation. Optimal dosage to ensure 50% growth and multiplication rates is estimated at 26 Gy for diploid clones and 16 Gy for haploid clones.

Seizures in Rats Associated with Divalent Cation Inhibition of Na+–K+-ATP'ase

1971 ◽  
Vol 49 (11) ◽  
pp. 1217-1224 ◽  
Author(s):  
J. Donaldson ◽  
T. St-Pierre ◽  
J. Minnich ◽  
A. Barbeau
Keyword(s):  
Divalent Cation ◽  
Regional Analysis ◽  
Intraventricular Injection ◽  
Specific Inhibition ◽  
Low Doses ◽  
High Doses ◽  
Very High

In vitro determination of rat brain microsomal ATP'ase activity revealed specific inhibition of the Na+–K+-ATP'ase by cations in the order Zn2+ > Cu2+ > Fe2+ > Mn2+. Intraventricular injection of the same cations or of ouabain resulted in convulsions. Regional analysis of ATP'ase from brains of rats after convulsions showed inhibited Na+–K+-ATP'ase activity in hippocampus and hypothalamus. Hippocampus and hypothalamus were found to have the highest Na+–K+-ATP'ase activity in the rat brain.The potent inhibitors of Na+–K+-ATP'ase in vitro (ouabain, Zn2+, and Cu2+) were similarly effective in vivo (hippocampus and hypothalamus), while the inhibitors relatively ineffective in vitro (Fe2+ and Mn2+) were similarly of low potency in vivo. The potent inhibitors of Na+–K+-ATP'ase caused convulsions at low doses; the ineffective inhibitors caused convulsions only at very high doses.

scholarly journals Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5699
Author(s):  
Amélie Foucault ◽  
Noémie Ravalet ◽  
Joevin Besombes ◽  
Frédéric Picou ◽  
Nathalie Gallay ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Low Dose ◽  
Low Doses ◽  
Aldehyde Dehydrogenase 2 ◽  
Primitive Hematopoiesis ◽  
In Vitro Effects ◽  
High Doses ◽  
Chlorpyrifos Ethyl ◽  
The Impact

(1) Background: The impact of occupational exposure to high doses of pesticides on hematologic disorders is widely studied. Yet, lifelong exposure to low doses of pesticides, and more particularly their cocktail effect, although poorly known, could also participate to the development of such hematological diseases as myelodysplastic syndrome (MDS) in elderly patients. (2) Methods: In this study, a cocktail of seven pesticides frequently present in water and food (maneb, mancozeb, iprodione, imazalil, chlorpyrifos ethyl, diazinon and dimethoate), as determined by the European Food Safety Authority, were selected. Their in vitro effects at low-doses on primary BM-MSCs from healthy volunteers were examined. (3) Results: Exposure of normal BM-MSCs to pesticides for 21 days inhibited cell proliferation and promoted DNA damage and senescence. Concomitantly, these cells presented a decrease in aldehyde dehydrogenase 2 (ALDH2: mRNA, protein and enzymatic activity) and an increase in acetaldehyde levels. Pharmacological inhibition of ALDH2 with disulfiram recapitulated the alterations induced by exposure to low doses of pesticides. Moreover, BM-MSCs capacity to support primitive hematopoiesis was significantly altered. Similar biological abnormalities were found in primary BM-MSCs derived from MDS patients. (4) Conclusions: these results suggest that ALDH2 could participate in the pathophysiology of MDS in elderly people long exposed to low doses of pesticides.

FACTORS AFFECTING THE INCORPORATION OF RADIOACTIVE PHOSPHATE INTO THE PHOSPHOLIPIDS OF SLICES OF CAT BRAIN

1954 ◽  
Vol 32 (1) ◽  
pp. 50-59 ◽  
Author(s):  
K. P. Strickland
Keyword(s):  
Oxygen Consumption ◽  
Inorganic Phosphate ◽  
Brain Slices ◽  
Phospholipid Fraction ◽  
Metabolic Inhibitors ◽  
Factors Affecting ◽  
Wide Range ◽  
Cat Brain

Slices of cat brain respiring in a Krebs–Ringer bicarbonate medium were found to incorporate radioactive inorganic phosphate (P32) into the phospholipid fraction. The addition of glucose or mannose increased the incorporation of P32 into the phospholipids. Fructose caused a small increase, whereas galactose was without effect. Pyruvate and lactate increased the incorporation of P32 into the phospholipids. Succinate, L (+)-glutamate, D (−)-glutamate, α keto-glutarate, citrate, and L-malate failed to support the incorporation.Anaerobic conditions and homogenization of the tissue prevented the in vitro incorporation of P32 into the phospholipids of cat brain. A wide range of metabolic inhibitors (cyanide, azide, malononitrile, chloretone, nembutal, iodoacetate, and fluoride), in concentrations that inhibit the oxygen consumption of brain slices, inhibited the incorporation. The incorporation was also inhibited by 2,4-dinitrophenol in concentrations that do not decrease the oxygen consumption of brain slices.These findings indicated that the incorporation of P32 into the phospholipids of slices of cat brain is a metabolic phenomenon and is dependent upon the maintenance of an adequate phosphorylating mechanism within the slice.

CYCLOOXYGENASE INDIPENDENT PLATELET AGGREGATION:RELATION WITH ASPI RIN CONCENTRATION

1987 ◽  
Author(s):  
C Cordova ◽  
F Violi ◽  
D Praticò ◽  
A Ghiselli ◽  
C Alessandri ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Low Doses ◽  
Dose Dependent Fashion ◽  
Threshold Doses ◽  
High Doses ◽  
Dose Dependent

Low doses of aspirin (20 mg/day) were previously reported to be uneffective in preventing platelet aggregation (PA) induced by pairs of aggregating agents such as PAF and adrenalin.This was in part attributed to the inability of such treatment to inhibit lipo oxygenase-dependent PA.The latter can be observed in vitro in"aspl rinated"platelets stimulated with high quantities of aggregating -agents.The aim of this study was to evaluate if the lipooxygenase-dependent PA was influenced by aspirin in a dose-dependent fashion. PA was studied in platelet rich plasma (PRP)(Born's method) by using threshold doses of aggregating agents (TDA) such as PAF(4-75 nM),epinephrine(0.6-2 μM) and collagen(2-4 μg/ml).PA performed in PRP pretrated with 100μM aspirin was fully prevented;in the same samples thromboxane (Tx) A2 evaluated by its metabolite Tx B2 was almost absent.Increasing amount of PAF(20 fold TDA),epinephrine(20 fold TDA) and collagen (36 fold TDA) do aggregate"aspirinated"pla telets;similarly"aspirinated"platelets aggregate when stimulated-with a pair of aggregating agents (TDA of PAF+epinephrine).This phenomenon was not detected if platelets were incubated with higher amounts of aspirin (250-500 μM).The study suggests that aspirin could influence lipooxygenase-dependent PA.This hypothesis is sup ported by a research showing the aspirin inhibits dose-dependently platelet HETE formation.A further study is now in progress to eva luate the influence of high doses of aspirin on cyclooxygenase-i"n dependent PA in vivo.

Drug uptake into everted intestinal sacs. II. Inhibition of secretion by hypertonicity.

1979 ◽  
Vol 236 (1) ◽  
pp. E57
Author(s):  
A Hurwitz
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Drug Uptake ◽  
Metabolic Inhibitors ◽  
Rat Jejunum ◽  
Intestinal Tissue ◽  
Active Secretion ◽  
Influx Rate

Mucosal hypertonicity, metabolic inhibitors, or absence of glucose and oxygen enhance mucosal-to-serosal influx of the cationic drug, pralidoxime (PAM), into sacs of everted rat jejunum in vitro. Conversely, efflux of PAM, which is twice the influx rate, is inhibited by mucosal hypertonicity or cyanide and iodoacetate. When sacs containing PAM, 0.87 mM, and glucose, 10 mM, were placed in identical drug- and sugar-containing mediums, the inside (serosal) concentration of PAM fell by over half in 120 min, whereas that of glucose more than doubled. Mucosal hypertonicity depressed PAM efflux and glucose influx regardless of serosal osmolarity. Although azide and mucosal hypertonicity each depressed glucose uptake and oxygen consumption while accelerating net PAM influx, azide more effectively depressed glucose and oxygen uptake, whereas hypertonicity caused greater acceleration of PAM uptake. Hypertonicity did not affect PAM binding to intestinal tissue. Varying mucosal pH did not change PAM or glucose uptake. Thus, mucosal hypertonicity apparently enhances net mucosal-to-serosal transfer of PAM by blocking its active secretion from serosa to mucosa.

scholarly journals Anti-Inflammatory Properties of Low and High Doxycycline Doses: AnIn VitroStudy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Roberta Di Caprio ◽  
Serena Lembo ◽  
Luisa Di Costanzo ◽  
Anna Balato ◽  
Giuseppe Monfrecola
Keyword(s):  
Gene Expression ◽  
Skin Diseases ◽  
High Dose ◽  
Low Doses ◽  
Dose Administration ◽  
Doxycycline Treatment ◽  
Anti Inflammatory ◽  
High Doses ◽  
Bacterial Resistances

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, ourin vitrostudy suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

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