Short- and Long-Term Effects of p-Ethynylphenylalanine on Brain Serotonin Levels

Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.     

The Effects of Leptin on Rat Brain Development; An Experimental Study

International Journal of Peptide Research and Therapeutics -     

Effects of Short- and Long-Term Protriptyline Treatment on Phospholipid Metabolism in Rat Brain

Wistar rats were injected intraperitoneally with 10 mg/kg of protriptyline according to one of the following schedules: a single dose or daily for 4 days (short-term), or daily for 2 or 13 weeks (long-term). Total lipid, total phospholipid, and individual phospholipid contents in the brain were determined. Further, the incorporation of 32P into individual phospholipids in vivo and the fatty acid composition of phosphatidylethanolamine in the brains of rats treated with protriptyline for 13 weeks were studied. Three alternative phases of changes of total and individual phospholipid contents in the brain during 13 weeks of experimentation were distinguished. An increase of phospholipid contents after 4 days, a decrease after 2 weeks, and a further increase after 13 weeks of protriptyline administration were found. However, phosphatidylinositol and phosphatidic acid levels after 13 weeks of protriptyline administration were diminished. The decrease of specific radioactivity of phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine and the increase of phosphatidylinositol, phosphatidic acid, and sphingomyelin in rats treated with the drug for a longer period of time were noted. No greater differences in fatty acid composition of phosphatidylethanolamine in the brains of the same group of rats were observed as compared to control. These results indicate that during long-term treatment with protriptyline the contents of lipids and phospholipids in rat brain are altered. The modification of the biological function of phospholipids in brain cell membranes is suggested.     

Long-Term Effects of RU24722 on Tyrosine Hydroxylase of the Rat Brain

The effects of RU24722 (14,15-dihydro-20,21-dinoreburnamine-14-ol) on tyrosine hydroxylase in central catecholaminergic neurons were studied in rats treated with different quantities of the molecule, and a time course was done for the minimal dose that gave the maximal effect. RU24722 induced increases in tyrosine hydroxylase activities and specific protein content in noradrenergic cells of the locus ceruleus and decreased all these parameters in dopaminergic neurons of the substantia nigra and ventral tegmental area. The results pointed out that the specific activity of newly synthesized tyrosine hydroxylase in the loci cerulei was potentially greater but was not expressed "in vivo" except 7 days after injection. The phenotypic specificity and the time course pattern of the action could be considered as a consequence of an induction mechanism. The comparison of long-term change in tyrosine hydroxylase values after piperoxane, RU24722, clonidine, and combined RU24722-clonidine treatment demonstrated that an activation during a few hours did not induce tyrosine hydroxylase in central noradrenergic neurons. Clonidine antagonized the activating effect of RU24722 following its injection but did not affect its long-term induction properties.     

Acute and Long-Term Effects of Chlorpromazine on Glutamine Synthetase and Glutaminase in Rat Brain

The effect of administration of chlorpromazine on the activity of glutamine synthetase and glutaminase and the content of glutamate and gamma-aminobutyric acid (GABA) in different regions of rat brain was studied in an investigation of the possible role of these amino acids in the lowering of the seizure threshold following prolonged administration of chlorpromazine. Chlorpromazine was administered at a dose of 20 mg/kg of body weight s.c. For the acute study, the animals were killed 20 min after a single injection. For the long-term study, the animals were treated every day with the same dose for 21 days and were killed 20 min after the last injection. The results showed an increase in glutamate level in each brain region investigated following long-term administration, but only in the cerebral cortex after a single dose. GABA levels showed an increase in the brainstem only in acute experiments. Glutamine synthetase activity was increased in all three regions after a single dose and only in cerebral cortex after long-term administration. Glutaminase activity showed a decrease in cerebral cortex only after long-term administration of the drug. These results suggest the possible occurrence of a state of increased excitability in the brain as a result of long-term administration of chlorpromazine, thus contributing to the known complication of seizures.     

Differential Effects of Long-Term Electroconvulsive Shock on Brain Levels of Enkephalin and Humoral-Endorphin

Abstract: Electroconvulsive shock (ECS) administrations repeated for 10 consecutive days cause an elevation in the opioid content of the rat brain. Two different endogenous opioids, enkephalin and humoral-endorphin, undergo independent changes that differ in both their time course and intracerebral localization. These metabolic changes parallel long-term behavioral modifications such as the development and dissipation of tolerance to the analgesic effect of ECS. The activation of two different, independent, endogenous opioid systems by ECS is in agreement with previous behavioral and pharmacological studies.     

Modelling the Long-Term Stabilization of Carbon from Maize in a Silty Soil

Soil organic carbon (SOC) models have been widely used to predict SOC change with changing environmental and management conditions, but the accuracy of the prediction is often open to question. Objectives were (i) to quantify the amounts of C derived from maize in soil particle size fractions and at various depths in a long-term field experiment using ¹³C/¹²C analysis, (ii) to model changes in the organic C, and (iii) to compare measured and modelled pools of C. Maize was cultivated for 24 years on a silty Luvisol which resulted in a stock of 1.9 kg maize-derived C m⁻² (36% of the total organic C) in the Ap horizon. The storage of maize-derived C in particle size fractions of the Ap horizon decreased in the order clay (0.65 kg C m⁻²) > fine and medium silt (0.43) > coarse silt (0.33) > fine sand (0.13) > medium sand (0.12) > coarse sand (0.06) and the turnover times of C₃-derived C ranged from 26 (fine sand) to 77 years (clay). The turnover times increased with increasing soil depth. We used the Rothamsted Carbon Model to model the C dynamics and tested two model approaches: model A did not have any adjustable parameters, but included the Falloon equation for the estimation of the amount of inert organic matter (IOM) and independent estimations of C inputs into the soil. The model predicted well the changes in C₃-derived C with time but overestimated the changes in maize-derived C 1.6-fold. In model B, the amounts of IOM and C inputs were optimized to match the measured C₃- and C₄-derived SOC stocks after 24 years of continuous maize. This model described the experimental data well, but the modelled annual maize C inputs (0.41 kg C m⁻² a⁻¹) were less than the independently estimated total input of maize litter C (0.63 kg C m⁻² a⁻¹) and even less than the annual straw C incorporated into the soil (0.46 kg C m⁻² a⁻¹). These results indicated that the prediction of the Rothamsted Carbon Model with independent parameterization served only as an approximation for this site. The total amount of organic C associated with the fraction 0–63 μm agreed well with the sum of the pools ‘microbial biomass’, ‘humified-organic matter’ and IOM of the model B. However, the amount of maize-derived C in this fraction (3.4 g kg⁻¹) agreed only satisfactorily with the sum of maize-derived C in the pools ‘microbial biomass’ and ‘humified organic matter’ (2.6 g kg⁻¹).     

Long-Term Effects of Chronic Light Pollution on Seasonal Functions of European Blackbirds (Turdus merula)

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems.     

Long-Term Treatment After Preoperative High-Dose Chemotherapy in a Lactating Breast Cancer Patient

Breast cancer during lactation is very rare, accounting for <3 % of all breast cancers. Its diagnosis and treatment is often delayed during pregnancy. We report a case of female lactating breast carcinoma in a 29-year old patient. The disease was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy and high-dose chemotherapy with peripheral blood stem cell support, followed by adjuvant chemotherapy and endocrine therapy. The metastases were detected 17 months after operation, palliative treatment including different chemotherapy for 60 cycles, locoregional radiotherapy and endocrine therapy. The total number of cycles of chemotherapy was 67, and the survival time was 118 months. We discuss the diagnosis and treatment options for breast cancer during lactation, based on a literature review.     

Detailed Characterization of Brain Dysfunction in a Long-Term Rodent Model of Critical Illness

Neurochemical Research - Critical illness encompasses a wide spectrum of life-threatening clinical conditions requiring intensive care. Our objective was to evaluate cognitive, inflammatory and...     

Effects of Fat-Enriched Diet on the Content of Sphingolipids in the Brain and on Cognitive Functions in Old Rats

It was demonstrated that levels of free fatty acids and radioactively labeled ([¹⁴C]) ceramide in the liver, muscles, and brain of rats fed a saturated fat-enriched diet for 36 weeks (from 15 to 24 months) increased, as compared with the corresponding levels in control animals of the same age (24 months old). A high-saturated fat diet resulted in a rise in the content of sphingolipids synthesized de novo in the neocortex and hippocampus of 24-month-old rats. High levels of ceramide and sphingosine in the neocortex and hippocampus induced in these rats by the above diet correlated with considerable worsening of the conditioned reflex activity of animals (reflex of active avoidance in the shuttle chamber).     

Long-Term Effects of Portacaval Anastomosis on the 5-Hydroxytryptamine, Histamine, and Catecholamine Neurotransmitter Systems in Rat Brain

Abstract: Portacaval anastomosis (PCA) in the rat is used as a model for portal systemic encephalopathy. Changes in the serotonergic, histaminergic, and catecholaminergic neurotransmitter systems are often found shortly after PCA. We have examined the long-term effects of PCA on the aminergic systems in brains of male Wistar rats, which 8 months previously had been subjected to PCA. Precursors, amines, and metabolites were assayed by HPLC. Eight months after PCA, the catecholamine levels were unchanged in all brain regions. In contrast, tryptophan was evenly increased throughout the brain. The accumulation of 5-hydroxytryptophan after decarboxylase inhibition (NSD-1015; 100 mg/kg i.p.) and the endogenous levels of 5-hydroxyindoleacetic acid were significantly higher in PCA rats, particularly in the hypothalamus and midbrain, whereas 5-hydroxytryptamine concentrations were unchanged. Histamine levels were elevated throughout the brain with the greatest increase found in the hypothalamus and in the striatum. tele -Methylhistamine levels were significantly elevated in cortex and hypothalamus. We conclude that 8 months after PCA, catecholaminergic systems had reestablished their homeostasis, whereas serotonergic and histaminergic systems still show profound disturbances in their function. With histamine, this is reflected as an increase in the amounts of both transmitter and metabolite; serotonergic neurons respond by increasing only the level of the metabolite.     

Long-Term,High-Dose Intravenous Immunoglobulin Therapy in a Patient with Banker-Type Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is a multisystem disease characterized by non-purulent inflammation in the striated muscle and skin. Banker-type JDM is difficult to treat and control, especially when it is a form that is resistant to steroid treatment. Here, we report a 2-year-old girl with Banker-type JDM resistant to steroid treatment. The patient received intravenous immunoglobulin (IVIg) at 400 mg/kg/5 days a week every 6 weeks. Motor function improved and the patient was able to walk after six cycles. IVIg was administered every four weeks for six cycles thereafter, and the patient was able to walk more quickly with an improvement in quality of life. No apparent adverse effects were observed during IVIg treatment.     

Effects of Exogenous Gonadal Steroids on Leptin Homeostasis in Rats

WU-PENG, SHARON, MICHAEL ROSENBAUM, MARGERY NICOLSON, STREAMSON C. CHUA, AND RUDOLPH L. LEIBEL. Effects of exogenous gonadal steroids on leptin homeostasis in rats. Obes Res. Background: In humans, circulating concentrations of the hormone leptin, normalized to body fat mass, are significantly higher in females compared to males. This experiment was designed to determine whether the administration of exogenous androgen or estrogen would significantly alter the relationship between plasma leptin and fat mass in rats. Methods: In the first experiment, plasma leptin and retro-peritoneal and parametrial (female)/epididymal (male) adipose tissue expression of leptin mRNA were measured in five male and five female 9. 5-week-old Sprague-Dawley rats. In a second experiment, gonadectomized 10. 5-week-old female Sprague-Dawley rats received 1 or 2 weeks of daily intraperitoneal injections (in oil) of 750 mg testosterone propionate, 2. 5 μg of estradiol benzoate or vehicle. At 0, 1, and 2 weeks, plasma concentrations of leptin, fat pad weight of parametrial and retroperitoneal fat pads, and leptin mRNA expression by Northern blot in retroperitoneal fat pads were determined. Daily weight and food intake of animals were monitored throughout the study. Results: Circulating leptin concentrations per unit of fat pad mass and leptin mRNA expression normalized to actin mRNA were higher in gonadally intact female compared to male rats. Compared to placebo, estrogen administration decreased food intake and body weight, but had no significant effect on leptin mRNA expression or on circulating leptin concentration. Testosterone administration increased body weight and decreased expression of leptin mRNA (only after 2 weeks), but did not change food intake or circulating leptin concentration. Conclusions: Administration of estrogen did not affect either leptin expression or the circulating concentration of leptin. Administration of androgen decreased expression of leptin mRNA. However, even after 2 weeks of testosterone administration to gonadectomized females, plasma leptin concentration, corrected for fat pad weight, was higher in gonadectomized females than in intact males, Thus, sex steroid-associated changes in plasma leptin concentration and leptin mRNA expression are not sufficient to explain the observed sexual dimorphism in plasma leptin concentrations in rats.     

Calcium Induces Long-Term Legacy Effects in a Subalpine Ecosystem

Human activities have transformed a significant proportion of the world’s land surface, with profound effects on ecosystem processes. Soil applications of macronutrients such as nitrate, phosphorus, potassium or calcium are routinely used in the management of croplands, grasslands and forests to improve plant health or increase productivity. However, while the effects of continuous fertilization and liming on terrestrial ecosystems are well documented, remarkably little is known about the legacy effect of historical fertilization and liming events in terrestrial ecosystems and of the mechanisms involved. Here, we show that more than 70 years after the last application of lime on a subalpine grassland, all major soil and plant calcium pools were still significantly larger in limed than in unlimed plots, and that the resulting shift in the soil calcium/aluminium ratio continues to affect ecosystem services such as primary production. The difference in the calcium content of the vegetation and the topmost 10 cm of the soil in limed vs. unlimed plots amounts to approximately 19.5 g m⁻², equivalent to 16.3% of the amount that was added to the plots some 70 years ago. In contrast, plots that were treated with nitrogen-phosphorus-potassium fertilizer in the 1930s did not differ from unfertilized plots in any of the soil and vegetation characteristics measured. Our findings suggest that the long-term legacy effect of historical liming is due to long-term storage of added calcium in stable soil pools, rather than a general increase in nutrient availability. Our results demonstrate that single applications of calcium in its carbonated form can profoundly and persistently alter ecosystem processes and services in mountain ecosystems.     

Behavioral Psychophysiological Intervention in a Mentally Retarded Epileptic Patient with Brain Lesion

Behavioral psychophysiological treatment entailing Slow Cortical Potential (SCP) biofeed-back training and behavioral self-control training was conducted with a 27-year-old male epileptic patient (seizures for 23 years) with Wechsler IQ 64 who underwent callosotomy. The patient had 12/week secondary generalized tonic-clonic seizures. The treatment, consisting of 43 SCP training sessions and 22 behavioral control sessions, yielded a highly significant reduction of seizure frequency to about 7.5/week; such a decrease had never been observed after administration of new anticonvulsant drugs, nor after the callosotomy. During SCP feedback training, the patient was able to produce highly-significant cortical differentiation of SCPs of about 4 µV. In addition, he developed several new behaviors indicating growing ability of self-perception and self-regulation. These findings suggest that a combination of SCP biofeedback with behavioral treatment of epilepsy can be used even in mentally retarded patients with organic brain disorders.