Severely Depleted Research Articles

Severe depletion of available deep soil water induced by revegetation on the arid and semiarid Loess Plateau

Revegetation-induced water deficits in the deep soil (>100 cm) on the arid and semiarid Loess Plateau threaten the sustainability of its ecosystems. However, quantifying changes in deep-soil water status at the regional scale remains challenging. This study represents the first attempt to integrate meta-analysis with the digitization of map data from previous research to evaluate the effects of revegetation on the deep soil water status. A total of 4906 observations from 94 peer-reviewed publications related to soil water changes to a depth of 500 cm in planted forests, planted shrublands, natural grasslands and croplands were synthesized, and two regional-scale evaluation criteria, the stable field capacity (SFC) and the permanent wilting point (PWP), were developed by digitizing the map data. The results indicated that (1) compared with cropland, revegetation more severely depleted the deep soil water availability, and planted forest revegetation resulted in the most serious depletion; (2) the extent of soil water changes was influenced significantly by the tree species planted; Platycladus orientalis was better able to maintain the deep soil water availability than Robinia pseudoacacia and Pinus tabuliformis; (3) the soil water status worsened with time after restoration, particularly at 20 years after restoration; (4) contrary to expectations, deep soil water depletion in forests and shrublands even increased in areas of high rainfall zones (>550 mm) compared to drier zones.; and (5) natural restoration (i.e., grasslands) was a better option than revegetation due to the resultant higher, more stable soil water availability. These results indicate that changes in deep soil water availability must be considered when planning revegetation initiatives.

Life history, distribution and seasonal movements of a threatened South African endemic seabream, Chrysoblephus gibbiceps

The red stumpnose Chrysoblephus gibbiceps (Sparidae) is a South African endemic seabream that has been severely depleted by fishing. A total of 678 C. gibbiceps were sampled by line and trawl fishing for a study of their morphology, age, growth, reproduction and diet. In addition, catch records from three time-periods since 1897 were interrogated for distribution patterns and movement behaviour. The sex ratio was 1.5:1 in favour of males. The length–weight relationship, W = 9.32 × 10−5 LF2.811, indicates hypoallometric growth. The bulbous head of large males is a secondary sexual characteristic. A von Bertalanffy growth model was fitted to age data obtained using otolith analyses: LF = 429.9 × (1 – e−0.113(t – (−3.799)). The maximum recorded age was 48 years, which is among the highest in seabreams, though the species matures after only 3 years. The gonadosomatic index (GSI) of ripe females (4.5%) was comparatively low, and the two-month-long early-summer spawning season was short compared with that of other sympatric seabreams. The very low GSI of ripe males (1.6%) suggests courtship battles and polygamy. The species feeds over low-profile reefs and consolidated sediments. The principal prey are ophiuroids. Although its trophic level is 3.7, C. gibbiceps has a low-nutrition diet. Historical and current catch data confirm a distribution from Cape Point (southeastern Atlantic) to southern KwaZulu-Natal Province (western Indian Ocean). There is evidence for localised migratory patterns, now partly lost due to severe population depletion. Whereas protogyny and resident behaviour have been suggested as traits that render seabreams vulnerable to fishing pressure, C. gibbiceps is a shoaling gonochorist that has collapsed due to fishing.

Ablation behavior of C/C-ZrC-SiC composites prepared by reactive melt infiltration under oxyacetylene torch at two heat fluxes

C/C-ZrC-SiC composites were prepared by reactive melt infiltration and tested using an oxyacetylene torch with the heat fluxes of 4.18 and 2.38 MW/m2. The results showed that compared to C/C and C/C-SiC at the heat flux of 4.18 MW/m2, the mass ablation rates of C/C-ZrC-SiC were decreased by 60.8% and 44.8%, respectively. Its linear ablation rate was 7.3% higher than that of C/C, but was 13.5% lower than that of C/C-SiC. The C-SiC matrix and fibers of C/C-SiC in the center region were severely depleted by the high ablation temperature. C/C-ZrC-SiC composites experienced the temperature exceeding 2400 °C associated with intense mechanical scouring of gas flow. The severe depletion of SiC and carbon fibers on the surface led to the formation of the porous ZrO2 layer. The spallation of ZrO2 occurred in the center of the ablated surface as a result of mechanical denudation of high temperature gas flow. At the heat flux of 2.38 MW/m2, the mass and linear ablation rates of C/C-ZrC-SiC were decreased by 76.8% and 88.4% (C/C), 66.9% and 58.3% (C/C-SiC), respectively. The oxide was slightly peeled off in the center region of C/C-SiC. The surface temperatures of C/C-SiC and C/C-ZrC-SiC were lower than that of C/C composites. The island-like ZrO2 and SiO2 layer were formed on the ablated surface of C/C-ZrC-SiC and acted as effective barriers to shield the ablation heat and slow inward transport of oxygen to the underlying material.

Calcium Influx through TRPV1 Inhibits Piezo Channels via Phosphoinositide Depletion

Capsaicin, the activator of the noxious heat sensor TPRV1 is clinically used to relieve chronic pain. Desensitization of TRPV1 involves downstream PLCδ activation, but the mechanism how capsaicin treatment can also alleviate mechanical allodynia is unknown. Piezo2 encodes rapidly adapting mechanically activated currents in sensory neurons. Expression of these novel mechanosensitive ion channels in a subset of TPRV1 positive neurons suggests their role in pain related sensory mechanotransduction.Our study shows that capsaicin application inhibited rapidly adapting mechanically activated currents in TRPV1 expressing sensory neurons. We also show that TRPV1 activation inhibited heterologously expressed Piezo1 and Piezo2 ion channels in whole-cell patch clamp experiments. Inclusion of either phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] or its precursor PI(4)P in the patch pipette alleviated this inhibitory effect. Activation of PLCβ by stimulating muscarinic receptors only marginally inhibited mechanically activated Piezo1 currents. Experiments using phosphoinositide sensors revealed that activation of PLCδ by a robust calcium influx through TRPV1 severely depleted PI(4,5)P2 and PI(4)P. On the other hand, muscarinic stimulation of PLCβ significantly decreased PI(4,5)P2 levels, but only induced a small decrease of PI(4)P. This differential activation of PLC isoforms may explain the difference between the inhibitory effects of these PLC pathways. Targeted depletion of PI(4,5)P2 and PI(4)P using a chemically inducible lipid phosphatase replicated the inhibition of Piezo1 currents. Additionally, PI(4,5)P2 and PI(4)P applied to excised inside-out patches inhibited the rundown of Piezo1 activity further emphasizing the significance of these phosphoinositides in Piezo channel regulation.Here we demonstrate that the activity of Piezo channels require the presence of either PI(4,5)P2 or PI(4)P and severe depletion of both phosphoinositides by TRPV1 activation limits channel activity. In conclusion our data may explain how capsaicin alleviates mechanically induced pain.

Comparative study of soil fertility status of cold desert Ladakh region before and after cloudburst

Present study was undertaken to determine loss of soil organic carbon, major and micronutrient status of cold desert Ladakh region as a result of unprecedented cloudburst in August 2010. Heavy rainfall (250 mm) within an hour leading to flash floods resulted in severe loss of standing crops spreading over 1400 ha of agriculture land besides destruction of human, animal lives, infrastructures. In most of the affected areas, top fertile soil completely washed away resulting in severe depletion of various major and micro nutrients essential for good soil health. Soil pH was recorded 8.66 and organic carbon severely depleted from 1.09% to only 0.24% making the soil very loose and poor in WHC. N, P and K (115.4, 1.0 and 103.4 kg/ha respectively) and micronutrient contents were also severelyreduced as compared to original soil. These losses have severe long-term effects on crop productivity and economy of the region. Some ameliorative measures have also been mentioned for improving soil health and sustainable crop production.

Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala

Most children with cancer live in developing countries where the prevalence of malnutrition may reach 50% and influence the course of the disease. This study examined the prevalence and severity of malnutrition at diagnosis, as well as after 3 and 6 months of chemotherapy, in children with acute lymphoblastic leukemia (ALL) in Guatemala. Triceps skin fold thickness (TSFT) and mid upper arm circumference (MUAC) provided measures of nutritional status (NS) in three categories: adequately nourished (A): TSFT and MUAC > 10th percentile; severely depleted (SD): TSFT or MUAC < 5th percentile; and moderately depleted (MD): all the remaining patients. Of 331 new patients, 241 had NS assessed at diagnosis. A = 113 (46.9%); MD = 28 (11.6%); SD = 100 (41.5%). At 3 months A = 106 (52.2%); MD = 25 (12.3%); SD = 72 (35.5%). At 6 months A = 146 (76.0%); MD = 12 (6.3%); SD = 34 (17.7%). In multivariate analysis, SD children at 6 months of treatment had a hazard of death that was 2.4-fold the hazard of those A or MD (95% CI: 1.3-4.7) Malnutrition is prevalent in newly diagnosed children with ALL in Guatemala and severe nutritional depletion is apparently predictive of abandonment of therapy and relapse of disease, but if children survive and improve their NS in the first 6 months after diagnosis, their chances of survival may improve significantly to approximate those in children not presenting with nutritional depletion.

UV radiation below an Arctic vortex with severe ozone depletion

Abstract. The erythemally weighted (UV) irradiance below the severely depleted Arctic vortices in spring 1996 and 1997 were substantially elevated. On average the UV increased 36 and 33% relative to the 1979-1981 mean assuming clear skies from day 80-100 in 1996 and 1997, respectively. On clear sky days large regions of the Arctic experienced maximum UV increases exceeding 70 and 50% on single days in 1996 and 1997, respectively. A minor fraction of these increases are not anthropogenic and have a dynamical origin as seen by comparison to 1982, when hardly any ozone depletion is expected.

Protection of rats against 3-butene-1,2-diol-induced hepatotoxicity and hypoglycemia by N-acetyl- l-cysteine

3-Butene-1,2-diol (BDD), an allylic alcohol and major metabolite of 1,3-butadiene, has previously been shown to cause hepatotoxicity and hypoglycemia in male Sprague–Dawley rats, but the mechanisms of toxicity were unclear. In this study, rats were administered BDD (250 mg/kg) or saline, ip, and serum insulin levels, hepatic lactate levels, and hepatic cellular and mitochondrial GSH, GSSG, ATP, and ADP levels were measured 1 or 4 h after treatment. The results show that serum insulin levels were not causing the hypoglycemia and that the hypoglycemia was not caused by an enhancement of the metabolism of pyruvate to lactate because hepatic lactate levels were either similar (1 h) or lower (4 h) than controls. However, both hepatic cellular and mitochondrial GSH and GSSG levels were severely depleted 1 and 4 h after treatment and the mitochondrial ATP/ADP ratio was also lowered 4 h after treatment relative to controls. Because these results suggested a role for hepatic cellular and mitochondrial GSH in BDD toxicity, additional rats were administered N-acetyl- l-cysteine (NAC; 200 mg/kg) 15 min after BDD administration. NAC treatment partially prevented depletion of hepatic cellular and mitochondrial GSH and preserved the mitochondrial ATP/ADP ratio. NAC also prevented the severe depletion of serum glucose concentration and the elevation of serum alanine aminotransferase activity after BDD treatment without affecting the plasma concentration of BDD. Thus, depletion of hepatic cellular and mitochondrial GSH followed by the decrease in the mitochondrial ATP/ADP ratio was likely contributing to the mechanisms of hepatotoxicity and hypoglycemia in the rat.

Modelling recruitment and abundance of Atlantic cod, Gadus morhua, in the eastern Skagerrak–Kattegat (North Sea): evidence of severe depletion due to a prolonged period of high fishing pressure

In exploited fish populations, most of the variance in stock size is attributed to highly variable recruitment. Understanding the recruitment process and how it relates to stock size (i.e. the often sought for stock-recruitment functions) and to environmental stochasticity is of central importance to fisheries science and management. However, in many, if not most, exploited marine fish populations, fishing mortality is the other major force affecting stock size. Here we explored the effects of several biotic and abiotic variables on Atlantic cod ( Gadus morhua ) recruitment and abundance in the eastern Skagerrak–Kattegat area by deploying a GAM (general additive model) type of modelling. It was recognised that fishing pressure and not variable environment via recruitment was the pivotal variable explaining the dynamic of the cod stocks. Due to a prolonged period of high fishing intensity, local cod stocks in the study area, such as the one in the Kattegat may be considered as severely depleted, or possibly, on the verge of total extinction. It was further observed that population biomass and recruitment were substantially uncoupled, which may be regarded as an effect of continued transportation of recruits from spawning aggregations in adjacent areas such as the North Sea.

Nutritional assessment: lean body mass depletion at hospital admission is associated with an increased length of stay

Low fat-free mass may be an independent risk factor for malnutrition that results in an increased length of hospital stay (LOS). The objectives were to compare differences in fat-free mass and fat mass at hospital admission between patients and healthy control subjects and to determine the association between these differences and the LOS. Patients (525 men, 470 women) were prospectively recruited at hospital admission. Height-corrected fat-free mass and fat mass (fat-free-mass index or fat-mass index; in kg/m2) were determined in patients at admission by bioelectrical impedance analysis and were compared with values for sex-, age-, and height-matched control subjects. Patients were classified as well-nourished, moderately depleted, or severely depleted on the basis of a Subjective Global Assessment questionnaire and a body mass index (in kg/m2) < or > 20. Low fat-free mass was noted in 37% and 55.6% of patients hospitalized 1-2 d and > 12 d, respectively. The odds ratios were significant for fat-free-mass index and were higher in patients with a LOS of > 12 d [men (odds ratio: 5.6; 95% CI: 3.1, 10.4), women (4.4; 2.3, 8.7)] than in those with a LOS of 1-2 d [men (3.3; 2.2, 5.0), women (2.2; 1.6, 3.1)]. Severe nutritional depletion was significantly associated only with a LOS > 12 d. Fat-free mass and fat-free-mass index were significantly lower in patients than in control subjects. Because the fat-free-mass index is significantly associated with an increased LOS, provides nutritional assessment information that complements that from a Subjective Global Assessment questionnaire, and is a more sensitive determinant of the association of fat-free mass with LOS than is a weight loss > 10% or a body mass index < 20, it should be used to evaluate nutritional status.

Tacrine inhibits topoisomerases and DNA synthesis to cause mitochondrial DNA depletion and apoptosis in mouse liver

After several weeks of treatment, levels of alanine aminotransferase (ALT) increase in 50% of patients treated with tacrine for Alzheimer's disease. We looked for progressive effects on DNA to explain delayed toxicity. We first studied the in vitro effects of tacrine on DNA replication and topoisomerase-mediated DNA relaxation. We then treated mice with doses of tacrine reproducing the human daily dose on a body area basis and studied the effects of tacrine administration for up to 28 days on hepatic DNA, mitochondrial function, and cell death. In vitro, tacrine impaired DNA polymerase γ-mediated DNA replication and also poisoned topoisomerases I and II to increase the relaxation of a supercoiled plasmid. In vivo, administration of tacrine markedly decreased incorporation of [ 3H]thymidine into mitochondrial DNA (mtDNA), progressively and severely depleted mtDNA, and partly unwound supercoiled mtDNA into circular mtDNA. Incorporation of [ 3H]thymidine into nuclear DNA (nDNA) was barely decreased, and nDNA levels were unchanged. After 12 to 28 days of treatment, administration of tacrine increased p53, Bax, mitochondrial permeability transition, cytosolic cytochrome c, and caspase-3 activity and triggered hepatocyte apoptosis and/or necrosis. In conclusion, the intercalating drug tacrine poisons topoisomerases and impairs DNA synthesis. Tacrine has been shown to accumulate within mitochondria, and it particularly targets mtDNA. After several weeks of treatment, the combination of severe mtDNA depletion and a genotoxic stress enhancing p53, Bax, and permeability transition trigger hepatocyte necrosis and/or apoptosis. (H epatology 2003;38:715-725.)

Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy/Liv mice.

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.

FIRE IMPACT ON A MAQUIS SOIL SEED BANK IN CABAÑEROS NATIONAL PARK (CENTRAL SPAIN)

The direct impact of fire on the soil seed bank and the changes observed one year later were studied by analysis of seed content in sample layers at depths of 0–2 cm and 2–5 cm. Fire had a severe but selective impact on the soil seed bank: species with transient seed reserves accumulating on the soil surface were eliminated, whereas species with persistent buried seed reserves tended to remain in the soil after the passage of fire. Thick seed coats were shown to be an efficient mechanical protection barrier to fire. One year after fire, trade-off between input and output into seed bank produced a conspicuous recovery of seed density and species richness on the soil surface, and a pronounced impoverishment in the 2–5-cm-depth soil layer. In general, seed banks of woody species were severely depleted due to the lack of replacement following fire, with the exception ofErica, which maintained a high seed bank density in the upper soil layer. The post-fire recovery of soil seed populations was mainly due to two clearly differentiated groups of annuals. The first group was of species whose seeds survived fire, germinated, and completed their phenological cycle. They were mainly fire-ephemerals. The second group consisted of wind-dispersed species whose soil seed banks had suffered a very severe (even total) depletion by fire. They were mainly Gramineae and Compositae species which behaved as opportunistic fire-sensitive invaders.

Disruption of the murine lecithin:cholesterol acyltransferase gene causes impairment of adrenal lipid delivery and up-regulation of scavenger receptor class B type I.

Lecithin:cholesterol acyltransferase (LCAT) is the major determinant of the cholesteryl ester (CE) content of high density lipoprotein (HDL) in plasma. The selective uptake of HDL-CE is postulated to participate in delivery of tissue-derived cholesterol both to the liver and steroidogenic tissues. Recent studies comparing mice with similarly low levels of HDL, due to the absence of either of the two major HDL-associated apolipoproteins apoA-I and apoA-II, suggest that apoA-I is crucial in modulating this process, possibly through interaction with scavenger receptor class B type I (SR-BI). Because of the central role of LCAT in determining the size, lipid composition, and plasma concentration of HDL, we have created LCAT-deficient mice by gene targeting to examine the effect of LCAT deficiency on HDL structure and composition and adrenal cholesterol delivery. The HDL in the LCAT-deficient mice was reduced in its plasma concentration (92%) and CE content (96%). The HDL particles were heterogeneous in size and morphology and included numerous discoidal particles, mimicking those observed in LCAT-deficient humans. The adrenals of the male Lcat (-/-) mice were severely depleted of lipid stores, which was associated with a 2-fold up-regulation of the adrenal SR-BI mRNA. These studies demonstrate that LCAT deficiency, similar to apoA-I deficiency, is associated with a marked decrease in adrenal cholesterol delivery and supports the hypothesis that adrenal SR-BI expression is regulated by the adrenal cholesterol.

Elimination of Duplicity in Nutrition Measures is Expected to Save the Trauma Patient Population > $ 18,000 Per Year

LEARNING OUTCOME: State the appropriateness of obtaining transferrin tests as a measure of nutritional status in trauma patients.A review of the literature suggests prealbumin (transthyretin) is better than transferrin for monitoring nutritional status. Elimination of routine transferrin tests may save money and remove problems with assessing nutritional status when prealbumin and transferrin results conflict. A retrospective analysis of data on trauma patients who were fed through enteral tubes was undertaken. A transferrin test was routinely ordered with each prealbumin test. Tests were paired if both prealbumin and transferrin were obtained from the same serum sample. Visceral protein status was determined by comparing patient values to reference ranges for normal, mild depletion, moderate depletion, and severe depletion. A total of 53 paired tests were collected on 22 patients and of these, 45 % yielded the same status ranking by both proteins. Transferrin results suggested a greater degree of depletion; 47 % vs. 25 % of patients were categorized as moderately to severely depleted, using transferrin and prealbumin, respectively. Savings would have ranged from $ 15 to $ 107 per patient if all transferrin labs had been eliminated resulting in mean savings of $ 37 per patient. On average, approximately 50 initial nutrition support notes are written in the trauma service each month. Elimination of one initial and one follow-up transferrin test per patient is expected to reduce charges by > $ 18,000 per year for this patient population. Routine ordering of transferrin tests have been eliminated. Transferrin tests were more likely to suggest a greater degree of visceral protein depletion than suggested by prealbumin. In addition, discontinuation of routine ordering of transferrin tests is expected to result in substantial reductions in yearly charges to the trauma patient population.

Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine depletions and parkinsonian symptoms

Studies in rodents suggest that PC12 cells, encapsulated in semipermeable ultrafiltration membranes and implanted in the striatum, have some potential efficacy for the treatment of age- and 6-OHDA-induced sensorimotor impairments (22, 70, 71, 74). The objectives of this study were to: (1) determine if baby hamster kidney cells engineered to secrete glial cell line-derived neurotrophic factor (BHK-GDNF) would survive encapsulation and implantation in a dopamine-depleted rodent striatum, (2) compare polymer-encapsulated PC12 and PC12A cells in terms of their ability to survive and produce catecholamines in vivo in a dopamine-depleted striatum, and (3) determine if BHK-GDNF, PC12, or PC12A cells reduce parkinsonian symptoms in a rodent model of Parkinson's disease. Capsules with BHK-GDNF or PC12 cells contained viable cells after 90 days in vivo, with little evidence of host tissue damage/gliosis. In rats with tyrosine hydroxylase (TH)-positive fibers remaining in the lesioned striatum, there was TH-positive fiber ingrowth into the membranes of the BHK-GDNF capsules. PC12-containing capsules had higher basal release of both dopamine and L-DOPA after 90 days in vivo than before implantation, while basal release of both dopamine and L-DOPA decreased in the PC12A-containing capsules. Both encapsulated PC12 and PC12A cells, but not encapsulated BHK-GDNF cells, decreased apomorphine-induced rotations. Parkinsonian symptoms (akinesia, freezing/bracing, sensorimotor neglect) related to the extent of dopamine depletion were evident even in rats with dopamine depletions of only 25%. Evidence that encapsulated cells may attenuate these parkinsonian symptoms was not detected but most of the rats were more severely depleted of dopamine than Parkinson's patients (less than 2% dopamine remaining in the entire striatum), and these tests were not sensitive to differences between rats with less than 10% dopamine remaining. These results suggest that cell encapsulation technology can safely provide site-specific delivery of dopaminergic agonists or growth factors within the CNS, without requiring suppression of the immune system, and without using fetal tissue. Of the three types of encapsulated cells examined in the present study, PC12 cells seem to offer the most therapeutic potential in rats with severe dopamine depletions.

Adenosine triphosphate depletion reverses sodium-dependent, neuronal uptake of glutamate in rat hippocampal slices

Extracellular accumulations of excitatory amino acids (EAAs) may mediate ischemic neuronal damage. Metabolic insults can decrease Na+ and K+ plasma membrane gradients, thereby reducing the driving force for uptake of EAAs into cells by Na(+)-dependent EAA cotransporters. EAA accumulations could result from decreased uptake and increased release due to reversal of these cotransporters. ATP depletion, uptake, and release of EAAs were measured by HPLC in slices treated with metabolic inhibitors. Inhibition and reversal of cotransporters were determined by uptake or release of D,L-threo-beta-hydroxyaspartate (OH-Asp), an EAA analog with high affinity for cotransporters. Moderate ATP depletion (7 > ATP nmol/mg protein > 3) reduced uptake by cotransporters without increasing release of EAAs. When ATP was severely depleted (ATP < 2 nmol/mg protein), increased release of EAAs and preloaded OH-Asp occurred, consistent with reversal of cotransporters. Release of glutamine and asparagine was not increased, confirming that release was not primarily due to nonselective increased membrane permeability. ATP depletion and ouabain acted synergistically to produce EAA release, strongly suggesting release was largely mediated by inhibition of Na/K-ATPases. Severe ATP depletion decreased glutamate-like immunoreactivity primarily in axonal terminal-like structures, suggesting release occurred primarily from terminals. Moderate ATP depletion may increase extracellular EAAs by decreasing uptake. Severe ATP depletion may further increase EAAs by reversing uptake, thereby releasing cytosolic neuronal pools of EAAs.

The 5,7-DHT-induced anticonflict effect is dependent on intact adrenocortical function

We have recently reported that the anxiolytic-like effect observed in rats severely depleted of brain serotonin (5-HT) by means of 5,7-DHT is indirect and probably involves the GABA A/benzodiazepine chloride ionophore receptor complex (GABA A/BDZ-RC). One tentative explanation for this effect considered the involvement of corticosteroids. In the present series of experiments we have therefore investigated the effect of adrenalectomy (ADX) on the 5,7-DHT-induced anxiolytic-like effect displayed by rats in Vogel's conflict test. ADX totally abolished the anticonflict effect of the 5,7-DHT lesion. Replacement treatment with corticosterone, but not with dexamethasone, reinstated the anticonflict effect. These results indicate that an intact adrenocortical function, possibly via brain steroid type I receptors, is required for the expression of the 5,7-DHT-induced anxiolytic-like effect. It is postulated that ADX lowers the concentration of endogenous positive modulators at the GABA A/BDZ-RC to a level no longer sufficient to produce anxiolytic-like effects in 5,7-DHT-lesioned animals. The finding that 5,7-DHT-lesioned animals were more sensitive than sham-lesioned controls to the anticonflict effect of the barbiturate-like corticosteroid THDOC provides further support for the contention that an increased endogenous activity at the GABA A/BDZ-RCes is involved in the anxiolytic-like effect observed in rats with a severe depletion of brain 5-HT.

Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum

The cocaine congener [3H]CFT, also designated [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyltropane), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiographic distribution of [3H]CFT binding (5 nM) in human postmortem control and Parkinson's-diseased striatal tissue sections was compared. In control tissue, high and comparable levels of [3H]CFT binding were observed in the putamen and caudate nucleus. At least 90-99% of total [3H]CFT bound was inhibited by (-)-cocaine (30 microM), suggesting that a high proportion of [3H]CFT is specifically bound. In Parkinson's-diseased tissue, binding sites for [3H]CFT were reduced by 80% in the caudate nucleus and 96% in the putamen. This pattern of depletion parallels the previously reported loss of dopamine in these brain regions (Kish, Shannak, and Hornykiewicz, New Engl. J. Med., 318:876-880, 1988). In the dorsal caudate nucleus of Parkinson's-diseased tissue, a lateral-to-medial gradient of [3H]CFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of [3H]CFT binding sites in Parkinson's diseased striatum supports the following conclusions: 1) the dopamine transporter is localized primarily on presynaptic nigrostriatal terminals; 2) in the caudate and putamen, cocaine recognition sites are associated primarily with the dopamine transporter; 3) the low level of nonspecific binding of [3H]CFT and the marked depletion of [3H]CFT-labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.

Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules

Metabolism and cellular levels of glycine, alanine, and other relevant amino acids in proximal tubules were studied during models of acute injury and protection by glycine. Freeze-clamped, normal rabbit renal cortex was very rich in glycine (66.8 nmol/mg protein) and glutamate and also had substantial levels of taurine, alanine, glutamine, serine, and aspartate. Isolated proximal tubules were severely depleted of all these amino acids (glycine, 2.1 nmol/mg protein). During 37 degrees C incubation in presence of alanine, tubules recovered only glutamate to a level approximating that in vivo (38.8 nmol/mg protein, 15.2 mM). Glycine added to medium at levels ranging from 0.25 to 2 mM was actively concentrated four- to sixfold by tubule cells. Two millimolar glycine potently protected tubules from lethal cell injury induced by hypoxia, antimycin A, or ouabain. Glycine levels of injured tubules rapidly equilibrated with medium, irrespective of whether glycine was loaded by preincubation or was added concomitantly with the injury maneuver. Metabolism of glycine during protection, assessed by changes in total levels, gas chromatography-mass spectroscopy determination of the fate of [13C]glycine, and redistribution of label from [3H]glycine was minimal. The data suggest that glycine plays an essential, constitutive role in maintenance of tubule cell structural integrity independently of common metabolic pathways. Intracellular amino acid content is sufficiently labile for depletion of structurally essential amino acids to potentially occur in a variety of settings, but, even with severe ATP depletion or Na+ pump inhibition, supplemental glycine is readily available to intracellular sites of action.