Uncoupling Factor Research Articles

Large Section of Soft Rock Gob-Side Entry Retaining Surrounding Rock Control

When cutting roof and pressure relief, the impact of blasting is especially obvious on the integrity of the roof of a large-section soft-rock roadway. The reasonable parameters of blasting roof cutting were studied through using Xiaohezui coal mine -12110 roadway as the engineering background. The LS-Dyna simulation results show that: Interval blasting is beneficial to the expansion of interhole cracks and the damage to the perimeter of the hole is smaller than that of adjacent blasting, the lower the charge uncoupling factor, the larger the perimeter of the hole fragmentation zone. The mechanical model of the large-section soft-rock roadway after retrieval was established, the support resistance equation of the roadway side support and the gangue in the extraction area was derived, and the minimum support force required for the roadway side support was solved. According to the site situation, the roadway support scheme for different areas was proposed, and after continuous delamination monitoring of the roof plate, it was found that the amount of roof-plate delamination was finally stabilized within 180 mm after the working face was advanced, and the effect of leaving the roadway was good.

Boosting of stable synchronization in coupled non-identical counter-rotating chaotic systems.

Achieving synchronization in coupled non-identical chaotic systems has been a difficult endeavor, and improving the stability of synchronization in such systems poses additional challenges. This research work addresses these challenges by identifying stable synchronization in coupled non-identical chaotic systems and enhancing its stability. The study explores chaotic attractors that arise from various system parameters to provide generalized results. Furthermore, the impact of the transient uncoupling factor on improving synchronization stability in coupled non-identical counter-rotating chaotic oscillators is discussed. By investigating these aspects, the research aims to contribute to the understanding and advancement of synchronization in coupled non-identical chaotic systems.

Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview.

Osteoporosis resulting from an imbalance of bone turnover between resorption and formation is a critical health issue worldwide. Estrogen deficiency following a nature aging process is the leading cause of hormone-related osteoporosis for postmenopausal women, while glucocorticoid-induced osteoporosis remains the most common in drug-induced osteoporosis. Other medications and medical conditions related to secondary osteoporosis include proton pump inhibitors, hypogonadism, selective serotonin receptor inhibitors, chemotherapies, and medroxyprogesterone acetate. This review is a summary of the cellular and molecular mechanisms of bone turnover, the pathophysiology of osteoporosis, and their treatment. Nuclear factor-κβ ligand (RANKL) appears to be the critical uncoupling factor that enhances osteoclastogenesis. In contrast, osteoprotegerin (OPG) is a RANKL antagonist secreted by osteoblast lineage cells. Estrogen promotes apoptosis of osteoclasts and inhibits osteoclastogenesis by stimulating the production of OPG and reducing osteoclast differentiation after suppression of IL-1 and TNF, and subsequent M-CSF, RANKL, and IL-6 release. It can also activate the Wnt signaling pathway to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts rather than adipocytes. Estrogen deficiency leads to the uncoupling of bone resorption and formation; therefore, resulting in greater bone loss. Excessive glucocorticoids increase PPAR-2 production, upregulate the expression of Dickkopf-1 (DKK1) in osteoblasts, and inhibit the Wnt signaling pathway, thus decreasing osteoblast differentiation. They promote osteoclast survival by enhancing RANKL expression and inhibiting OPG expression. Appropriate estrogen supplement and avoiding excessive glucocorticoid use are deemed the primary treatment for hormone-related and glucocorticoid-induced osteoporosis. Additionally, current pharmacological treatment includes bisphosphonates, teriparatide (PTH), and RANKL inhibitors (such as denosumab). However, many detailed cellular and molecular mechanisms underlying osteoporosis seem complicated and unexplored and warrant further investigation.

Inducement and enhancement of synchronization stability by transient uncoupling in coupled chaotic systems with inherent frequency parameters

In this paper, we explore the inducement of synchronization by transient uncoupling observed in unidirectionally coupled chaotic systems with inherent frequency parameters. The emergence of desyncronization with increase in frequency factor for fixed values of coupling strength and the suppression of stable synchronization to lower values of coupling strength in the presence of frequency factors are identified. The inducement of complete synchronization using the method of transient uncoupling in coupled Rossler systems and Chua’s circuit systems with frequency parameters incorporated in their system equations is reported. The enhancement of synchronization stability over greater values of coupling strength and frequency factors on the introduction of the transient uncoupling factor is studied.

Study on the disaster reduction mechanism of presplitting blasting and reasonable blasting parameters for shallowly buried remnant pillars

AbstractDisasters such as support crushing easily occur at the mining face under a shallowly buried remnant pillar; therefore, a method for presplitting blasting remnant pillars to relieve stress concentrations and reduce disaster occurrence is proposed. Based on the geological conditions of Nanliang Mine, combining theoretical analysis and numerical simulation to study the bearing characteristics and stress distribution characteristics of remnant pillars, the influence mechanism of presplitting blasting on remnant pillars in terms of the uncoupling factor, axial charge factor, blast hole arrangement, and detonation method is analyzed, revealing the presplitting blasting and disaster reduction mechanism of shallowly buried remnant pillars; furthermore, reasonable blasting parameters are determined. The results show that the rock is affected by the concentrated load within 40 m below the coal pillar; the reasonable blasting parameters are the uncoupled charge coefficient of 1.5, the axial charge factor of 1.0, and the simultaneous detonation of staggered holes. Blasting coal pillars can reduce the transmission effect of the overlying load and ensure the safe use of low‐resistance hydraulic support.

WATER DEMAND, CROP COEFFICIENT AND UNCOUPLING FACTOR OF COWPEA IN THE EASTERN AMAZON

ABSTRACT Cowpea has great socioeconomic importance in the northeastern part of Pará state. However, in order to provide suitable irrigation management during the dry period this region requires solid information regarding water demand by regional crops. This research aims to determine the water demand, the crop coefficient (Kc) and the uncoupling factor during the different development stages of cowpea in the northeast of Pará. The crop evapotranspiration (ETc) was measured by drainage lysimeters. This information was coupled to the reference evapotranspiration (ETo) to obtain the crop coefficients, which were used to adjust the model function of accumulated degree-days and the leaf area index (LAI). The uncoupling factor was estimated to indicate the factors that control evapotranspiration. The ETc values reached a cumulative total of 267.73 mm ± 10.21 mm during the cowpea cycle. The average value of the uncoupling factor was 0.66. This indicates that the cowpea crop does not fully uncouple from the atmosphere underneath the climatic conditions in northeast Pará. The cowpea Kc values presented averages of 0.8, 1.4 and 0.8 in the vegetative phase, reproductive phase and final stage, respectively. The Gaussian model showed an excellent fit for the estimation of Kc values based on accumulated degree days and the LAI. These amounts differ from others found in the literature. Therefore, it reinforces the necessity for an assessment of crop coefficients under local conditions and for the employment of more precise methods.

Erythrocyte fatty acid composition does not influence levels of free, bioavailable, and total 25-hydroxy vitamin D

In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6 ± 2.0 years) total 25(OH)D was measured by LC-MS/MS (n = 78), free 25(OH)D with ELISA (n = 64 of 78), and bioavailable 25(OH)D was calculated. Analysis of ery-FA composition was by gas chromatography (n = 56 of 78). A strong correlation between total 25(OH)D and free 25(OH)D was seen (r = .66, p < .001), and between total-25(OH)D and bioavailable 25(OH)D (r = .68, p < .001). No correlations between 25(OH)D fractions and specific fatty acids were found, and in particular, no associations with mono- and poly-unsaturated FA compositions. All 25(OH)D fractions were correlated with leptin (total 25(OH)D (r = −.33, p < .003); bioavailable 25(OH)D (r = −.47, p < .001); free 25(OH)D (r = −.44, p < .001). Associations were found between PTH and total 25(OH)D (r = −.35, p = .002) and weaker between bioavailable 25(OH)D (r = −.35, p = .040) and free 25(OH)D (r = −.28, p = .079). All fractions of 25(OH)D appear to correlate in a similar way to PTH, BMI and body fat (leptin). No association was found between ery-FA composition and free/bioavailable 25(OH)D. It is unlikely that FAs are a strong uncoupling factor of DBP-bound 25(OH)D.

Improvement of skeletal fragility by teriparatide in adult osteoporosis patients: a novel mechanostat-based hypothesis for bone quality.

SKELETAL ADAPTATION TO MECHANICAL STRAIN IN HUMANS Several lines of clinical evidence (1–3) suggest that the adult skeleton in humans continuously responds to change in mechanical environment to maintain resultant “elastic” deformation (strain) of bone; increased or decreased bone strain would normally induce bone gain or loss, respectively. Indeed, skeletal adaptation to mechanical strain, known as the mechanostat (4–6), plays a significant role in the treatment of osteoporosis. For example, bone strain from habitual physical activity decreases when an osteoporosis drug increases bone strength, indicating that the effect of osteoporosis therapy is limited by mechanical strain-related feedback control; this mechanostat-based logic is consistent with various clinical data (3). Approaches to reduce the limitation of osteoporosis therapy include pharmacologically enhancing skeletal response to mechanical loading, and earlier experimental studies using external mechanical loading models show that intermittent treatment with parathyroid hormone has such a possibility (7, 8). Importantly, treatment with teriparatide could synergistically produce bone gain with even low, physiological levels of mechanical loading in humans (9) as well as animals (10). The present article concisely discusses the effects of daily or weekly treatment with teriparatide and proposes a new mechanostat-based hypothesis for bone quality associated with mineral versus collagen. DAILY OR WEEKLY TREATMENT WITH TERIPARATIDE IN OSTEOPOROSIS In Japan, not only daily subcutaneous injection of teriparatide (20 μg/day) (11– 13) but also weekly subcutaneous injection of teriparatide (56.5 μg/week) (14, 15) has been approved for the treatment of adult osteoporosis patients with high risk of fracture. Interestingly, there are marked differences in the effects of these two treatments on circulating markers of bone formation and resorption. The daily injection results in a rapid and sustained increase in bone formation markers followed by a delayed increase in bone resorption markers (12); the period of time during which the increase in bone formation is superior to that in bone resorption is called the anabolic window (16). In contrast, the weekly injection induces only a transient increase in bone formation markers without an increase in bone resorption markers (14). Formation and resorption occur on different surfaces during bone modeling, and thus modeling-based bone formation and resorption are not coupled; such uncoupling factors include mechanical loading that stimulates bone formation and suppresses bone resorption. Modeling-based bone formation by histomorphometry (17, 18) as well as an increase in bone formation markers and a decrease in bone resorption markers in blood (19) are observed during the first month of daily treatment with teriparatide, which is consistent with clinical finding suggesting that daily treatment with teriparatide and normal physical activity synergistically produce bone gain (9). A rapid but transient increase in bone formation markers without an increase in bone resorption markers (14) implies that weekly treatment with teriparatide also stimulates modeling-based bone formation. On the other hand, long-term daily, but not weekly, treatment with teriparatide causes increases in both bone formation and resorption markers (12, 14). These systemic changes agree with histomorphometric data showing that 1 or 2 years of daily treatment with teriparatide results in an increase in remodeling-based bone formation (20); resorption followed by formation occurs on the same surface during bone remodeling and thus remodelingbased bone resorption and formation are coupled. Increased or decreased bone remodeling lowers or raises, respectively, the degree of mineralization (21), and cortical volumetric bone mineral density (BMD) is decreased after daily treatment with teriparatide (13). In contrast, weekly treatment with teriparatide is unlikely to increase bone remodeling because neither an increase in bone resorption markers nor a decrease in cortical volumetric BMD is not found (14, 15).

In Vitro Effects of Strontium on Proliferation and Osteoinduction of Human Preadipocytes.

Development of tools to be used for in vivo bone tissue regeneration focuses on cellular models and differentiation processes. In searching for all the optimal sources, adipose tissue-derived mesenchymal stem cells (hADSCs or preadipocytes) are able to differentiate into osteoblasts with analogous characteristics to bone marrow mesenchymal stem cells, producing alkaline phosphatase (ALP), collagen, osteocalcin, and calcified nodules, mainly composed of hydroxyapatite (HA). The possibility to influence bone differentiation of stem cells encompasses local and systemic methods, including the use of drugs administered systemically. Among the latter, strontium ranelate (SR) represents an interesting compound, acting as an uncoupling factor that stimulates bone formation and inhibits bone resorption. The aim of our study was to evaluate the in vitro effects of a wide range of strontium (Sr2+) concentrations on proliferation, ALP activity, and mineralization of a novel finite clonal hADSCs cell line, named PA20-h5. Sr2+ promoted PA20-h5 cell proliferation while inducing the increase of ALP activity and gene expression as well as HA production during in vitro osteoinduction. These findings indicate a role for Sr2+ in supporting bone regeneration during the process of skeletal repair in general, and, more specifically, when cell therapies are applied.

Alterations of mitochondria in liver but not in heart homogenates after treatment of rats with benznidazole

The mitochondrial oxidative phosphorylation system was studied in liver and heart homogenates after treatment of rats with benznidazole. The drug was given by oral gavage to adult female Wistar rats for 9 consecutive days (100 mg benznidazole/kg body weight as a daily dose). The mitochondrial state 4 and state 3 respiration rates, respiratory control, efficiency of oxidative phosphorylation (ADP/O), and ATPsynthase activity were assayed. The results showed that according to all these parameters, the mitochondria in cardiac homogenates were not affected in the rats treated with benznidazole. By contrast, mitochondria in the liver homogenates of drug-treated rats were altered, showing decreased respiratory control and a lower coefficient of ADP/O as a result of an increase in the state 4 respiration rate. These data indicate the possibility of production of an uncoupling factor leading to increased proton leakage through the inner mitochondrial membrane as a result of a 9-day treatment of rats with benzonidazole. The obtained experimental data might at least partly explain the nature of benznidazole toxicity in the liver treated with benznidazole.

Brown adipose tissue: the molecular mechanism of its formation

The function of brown adipose tissue (BAT) is to oxidize fat and to dissipate the energy produced as heat, providing a source of heat to the organism. Preadipocytes are stimulated by expression of the PRDM16 gene to differentiate into BAT cells. The PRDM16 protein is greatly enriched in BAT and causes increased expression of mitochondrial genes and greater density of mitochondria. It increases expression of the uncoupling factor UCP1 and thereby causes a large stimulation of uncoupled respiration with resultant heat production, enhanced by cAMP. Recent evidence strongly supports the idea that the PRDM16 gene determines BAT identity.

Parameter optimization of the slope pre-splitting blasting

Pre-splitting blasting is often used in slope engineering construction, pre-splitting parameters have important effects on reducing blasting vibrations. Pre-splitting blasting experiments were carried out to obtain normal pre-splitting blasting parameters such as hole diameter, hole space, gunpowder charge line density, and uncoupling factor. Ideal pre-splitting blasting parameters for four different hole diameters gained by the code ANSYS/LS-DYNA agree with the blasting experiments. By regression analysis, a simple fomula was given to choose the pre-splitting blasting parameters and to guide the succedent construction. Practice shows that combination of blasting experiments and numerical simulations is helpful to optimize pre-splitting blasting parameters.

The sensitivity of Cockayne's syndrome cells to DNA-damaging agents is not due to defective transcription-coupled repair of active genes.

Two of the hallmarks of Cockayne's syndrome (CS) are the hypersensitivity of cells to UV light and the lack of recovery of the ability to synthesize RNA following exposure of cells to UV light, in spite of the normal repair capacity at the overall genome level. The prolonged repressed RNA synthesis has been attributed to a defect in transcription-coupled repair, resulting in slow removal of DNA lesions from the transcribed strand of active genes. This model predicts that the sensitivity of CS cells to another DNA-damaging agent, i.e., the UV-mimetic agent N-acetoxy-2-acetylaminofluorene (NA-AAF), should also be associated with a lack of resumption of RNA synthesis and defective transcription-coupled repair of NA-AAF-induced DNA adducts. We tested this by measuring the rate of excision of DNA adducts in the adenosine deaminase gene of primary normal human fibroblasts and two CS (complementation group A and B) fibroblast strains. High-performance liquid chromatography analysis of DNA adducts revealed that N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) was the main adduct induced by NA-AAF in both normal and CS cells. No differences were found between normal and CS cells with respect to induction of this lesion either at the level of the genome overall or at the gene level. Moreover, repair of dG-C8-AF in the active adenosine deaminase gene occurred at similar rates and without strand specificity in normal and CS cells, indicating that transcription-coupled repair does not contribute significantly to repair of dG-C8-AF in active genes. Yet CS cells are threefold more sensitive to NA-AAF than are normal cells and are unable to recover the ability to synthesize RNA. Our data rule out defective transcription-coupled repair as the cause of the increased sensitivity of CS cells to DNA-damaging agents and suggest that the cellular sensitivity and the prolonged repressed RNA synthesis are primarily due to a transcription defect. We hypothesize that upon treatment of cells with either UV or NA-AAF, the basal transcription factor TFIIH becomes involved in nucleotide excision repair and that the CS gene products are involved in the conversion of TFIIH back to the transcription function. In this view, the CS proteins act as repair-transcription uncoupling factors. If the uncoupling process is defective, RNA synthesis will stay repressed, causing cellular sensitivity. Since transcription is essential for transcription-coupled repair, the CS defect will affect those lesions whose repair is predominantly transcription coupled, i.e., UV-induced cyclobutane pyrimidine dimers.

The immunoglobulin mu enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation.

Factor access in chromatin has been proposed to be facilitated by transcriptional enhancers. With the aim of uncoupling factor access from transcriptional stimulation by protein-protein contacts, we analyzed the potential of enhancer fragments to confer accessibility upon a linked promoter for prokaryotic T7 RNA polymerase. Access to the T7 promoter in pre-B cells from transgenic mice was examined by transcribing chromatin of isolated nuclei with T7 RNA polymerase. A 95-bp immunoglobulin mu enhancer core element was necessary and sufficient to confer accessibility upon the T7 promoter independent of its chromosomal position. This enhancer-dependent factor access could be uncoupled from an active transcriptional state of the transgene and was not accompanied by the formation of pronounced DNase I hypersensitive sites. Additional mu enhancer sequences comprising previously identified matrix attachment regions and a cryptic promoter were required to induce DNase I hypersensitivity. Together, these data provide evidence that the 95-bp mu enhancer core can establish localized factor access in nuclear chromatin independent of detectable transcription by endogenous polymerases and suggest that multiple steps are involved in the alteration of chromatin structure.

Loss of mitochondrial respiratory function and its suppression during cold ischemic preservation of rat livers with University of Wisconsin solution.

Preservation of the liver involves a period of cold (0 degrees to 4 degrees C) ischemia; the longer the ischemic period, the greater the injury to the liver. The mechanisms for cold-induced ischemic injury are not known, but it is clear that after preservation the liver has a reduced capacity to regenerate high-energy phosphate compounds (ATP). One cause for the delayed rate of ATP synthesis could be injury to the mitochondria. The effects of long-term (more than 24 hr) preservation on liver mitochondrial function have not been previously studied. In this study, rat livers were preserved in University of Wisconsin solution at 4 degrees C for up to 96 hr. After preservation, mitochondrial respiratory function was assayed in a homogenate and in isolated mitochondria. We saw a progressive increase in oligomycin-sensitive respiration with time of preservation (from 1.2 +/- 0.09 mumol.min-1.gm tissue-1 at 0 hr to 3.8 +/- 0.2 mumol.min-1.gm tissue-1 after 96 hr). The increase after 24-hr preservation (2.1 +/- 0.2 mumol.min-1.gm tissue-1) was also significantly greater than 0 time values (p less than 0.05). No decrease was found in uncoupler-stimulated respiration for up to 48 hr of preservation; only a small decrease was seen after 72 hr of preservation (about 30%). The cause of the increase in oligomycin-sensitive respiration appeared to be related to free fatty acids (or another uncoupling factor) generated during preservation. This was suggested from the fact that bovine serum albumin prevented the increase in oligomycin-sensitive respiration after all periods of preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Postprandial changes in intestinal slow-wave propagation reflect a decrease in cell coupling.

The purpose of these studies was to determine the effects of feeding on jejunal slow-wave propagation velocity (SWPV). Nine cats were instrumented with six pairs of electrodes implanted 4 cm apart on the jejunum. Electrical activity was recorded at the end of an 18-h fast after which each animal was fed 60 g of canned cat food. Recordings were continued during feeding and for several hours thereafter. This procedure was repeated at least twice for each cat. Average SWPV (cm/s) decreased from a fasting level of 2.28 +/- 0.20 (mean of means +/- SE) to 1.93 +/- 0.16 at 10-20 min, 1.51 +/- 0.11 at 1 h, and 1.37 +/- 0.10 at 3 h postprandially. Corresponding SW frequencies (SWFs) were 19.6 +/- 0.3, 18.7 +/- 0.2, 19.2 +/- 0.2, and 19.0 +/- 0.2 cycles/min, respectively. The differences between the fasting SWPV and that at 1 and 3 h were significant (P less than 0.05). When SWPV was plotted as a function of SWF, the slopes of the corresponding curves were also found to decrease postprandially (P less than 0.05, fasting vs. 1 and 3 h). There was no apparent change in SW amplitude, maximum rate of SW depolarization, or threshold. In the absence of changes in these parameters, the divergence of the slopes at lower SWFs indicates that the decrease in SWPV is because of increased internal resistance, probably the result of uncoupling of intestinal muscle cells. The change is rapid in onset and long in duration, suggesting that an uncoupling factor is released during ingestion of a meal, and that its effect persists for several hours.

Effect of immune cytokines on bone.

The effect of the bone resorptive cytokines IL-1 alpha, IL-1 beta, and TNF on bone formation was studied in an in vitro system. All three cytokines were profoundly inhibitory, with the rank order of potency IL-1 beta greater than IL-1 alpha greater than TNF. Inhibition was mediated by a depression of differentiated osteoblast functions, including alkaline phosphatase expression and matrix synthesis. Osteoblast proliferation was not affected. Bone formation inhibition was independent of PGE2 production, indicating a direct effect of cytokines on osteoblasts. High concentrations of IL-1 beta (10 U/ml) abrogated IGF-1-stimulated bone formation, providing evidence for the hypothesis that cytokines act as 'uncoupling factors'. Conversely, high concentrations of IGF-1 circumvented inhibition by IL-1 beta (0.1-1.0 U/ml). The interaction of cytokines and bone growth factors with osteoblasts are likely to be of critical importance in the regulation of bone mass at local inflammatory sites.

Bovine Milk-Associated Calcium as an Uncoupling Factor of Mitochondrial Respiration

Attempts to obtain coupled mitochondria from lactating bovine mammary tissue proved unsuccessful. To ascertain the nature of the uncoupling factor(s) responsible, we chose mitochondria of rat liver as a test system for their established isolation with retention of coupled respiration.Isolated, coupled rat liver mitochondria were uncoupled immediately by addition of microliter amounts of bovine milk and aqueous milk fractions. Dialysis of whey resulted in loss of the uncoupling factor, whereas boiling did not prevent the uncoupling effect. Inclusion in whey of the calcium chelator ethylene glycol-bis-(β-aminoethyl ether)-N,N′-tetraacetic acid protected rat liver mitochondria from the uncoupling effect. Mitochondrial swelling paralleled whey-induced respiratory uncoupling. When monitored by both oxygen consumption and swelling experiments, loss of respiratory control was correlated with the ionic calcium content of bovine milk. These findings suggest that high ionic calcium in bovine milk caused uncoupling.Extensive washings to remove or chelate calcium or inhibit mitochondrial calcium uptake were ineffective in preventing bovine mammary mitochondrial uncoupling. The implications of these findings suggest large amounts of compartmentalized intracellular calcium in bovine mammary tissue.

Effect of polyamine on microsomal cytochrome P-450 stimulation of rate and improved coupling of NADPH oxidation to hydroxylation

Low concentration of polyamine (50 μM spermine) significantly stimulated (3 to 4 folds) hydroxylation of benzphetamine and 7-ethoxycoumarin by liver microsomes and a reconstituted P-450 system. Level and concentration dependence of this activation depended both on the type of P-450 used in the. reconstituted system (LM 2 or LM 4) and on the substrate. NADPH oxidation and substrate hydroxylation were not stimulated to the same extent. Polyamines are therefore coupling or uncoupling factors in hydroxylation reactions depending on the experimental conditions.

RELATIONSHIP BETWEEN CEREBRAL ENERGY FAILURE AND FREE FATTY ACID ACCUMULATION FOLLOWING PROLONGED BRAIN ISCHEMIA

Prolonged ischemia by bilateral carotid artery ligation in rats resulted in cerebral edema with a reduced energy state. Mitochondria isolated from the ischemic brain showed an impairment of oxidative phosphorylation. The ischemic brain was also characterized by remarkable accumulation of free fatty acids known to have properties as an uncoupling factor. The major components of increased free fatty acids were palmitic, stearic, oleic and arachidonic acids. The analysis of saponified myelin and mitochondrial lipids from the ischemic brain showed a decrease in fatty acid contents. The main components of decreased fatty acids in these subcellular fractions corresponded to those of free fatty acids accumulating in the ischemic brain. These results indicate that cerebral energy failure in the ischemic brain is related to the accumulation of free fatty acids, which are derived from endogenous brain lipids.