Subchronic Intake Research Articles

Induction of erythropoietin by dietary medium-chain triacylglycerol in humans.

Erythropoietin (EPO) is pivotal in regulating red blood cell (erythrocyte) concentrations and is primarily synthesized in the kidney. Recent research has unveiled a possible link between elevated circulating concentrations of ketone bodies (KB) and circulating EPO concentrations; however, it is not known whether nutritionally induced endogenous ketogenesis can be a stimulus to induce EPO in humans. Therefore, this study aimed to assess whether acute and chronic intake of medium-chain fatty acid-containing triacylglycerol (MCT), which rapidly enhances endogenous circulating KB, would elevate circulating EPO concentrations in humans, as indicated by prior work with exogenous KB administration. The study followed a crossover design involving 16 young men undergoing two 8-day MCT or energy-matched long-chain fatty acid-containing triacylglycerol (LCT) interventions in a randomized order. Five-hour test days were performed before and after each intervention, in which circulating KB and EPO concentrations as well as hematological parameters were assessed. Acute intake of MCT yielded a 222% sustained 5-h elevation in KB concentrations compared with LCT-with notable peak values of 0.7 ± 0.1 mmol·L-1 (312% above basal values). Remarkably, within just 8 days of daily MCT intake an impressive 38% increase in basal, fasting plasma EPO concentrations (7.19 ± 1.14 to 9.91 ± 1.25 mIU·mL-1) was demonstrated. In conclusion, this study unveils a novel physiological stimulus of circulating EPO concentrations in humans, potentially offering a new dietary approach to counter anemia in cardiovascular diseases.NEW & NOTEWORTHY This study is the first to assess the effects of nutritionally induced ketogenesis by acute and subchronic intake of medium-chain fatty acids on plasma erythropoietin concentrations. Medium-chain fatty acid intake increases postprandial ketone body concentrations and within only 8 days of daily intake substantially enhances basal plasma erythropoietin concentrations in young men. We therefore reveal a dietary stimulus of endogenous circulating erythropoietin concentrations in humans, with the potential to counter anemia in cardiovascular diseases.

Leukocyte profile of laying hens’ blood under subchronic intake of sodium bromide with feed

The optimal physiological development and productivity of poultry depends on the intake of essential macroand microelements at levels that ensure the safety and quality of the resulting products (meat and eggs). It is important to note that both a lack and an excess of elements can lead to organ and system dysfunction. For instance, even small doses of bromine can cause hepatocyte dysfunction and disruptions to the endocrine and genitourinary systems. Additionally, the ability of these elements to accumulate in eggs and meat makes the products potentially dangerous for human consumption. Our work aimed to investigate the blood leukocyte profile of laying hens under subchronic intake of sodium bromide with feed and calculate integral leukocyte indices that allow assessing the state of the immune system and the degree of endogenous intoxication of the body. We also aimed to determine the strategy for further therapeutic or preventive measures. It was found that the intake of sodium bromide (by bromine) in the body of laying hens for 28 days in doses of 10.0 mg/kg, 50.0 mg/kg, and 250.0 mg/kg of feed leads to a significant increase in the Krebs index, leukocyte intoxication index, leukocyte shift index. This indicates changes in the functional activity of the immune system with the activation of the humoral immune system and decompensation of endogenous intoxication caused by the toxic effects of bromine. The significant decrease in the leukocyte index, neutrophil-monocyte ratio index, lymphocyte-monocyte ratio index, allergy index, and immunoreactivity index indicates a disruption in the interaction between the affective and effector links of immunity. This could potentially lead to cytokine deficiency, a reduction in the level of phagocytic defense, and an increased risk of immediate hypersensitivity.

The Effect of a High-Protein Diet Supplemented with Blackthorn Flower Extract on Polyphenol Bioavailability and Antioxidant Status in the Organs of C57BL/6 Mice.

The health benefits of polyphenols are based on their bioavailability, which is why a significant portion of research focuses on factors that affect their bioavailability. Previous studies suggest that the intake of polyphenols along with macronutrients in food represents one of the key factors influencing the bioavailability of polyphenols and, consequently, their biological activity in the organism. Since polyphenols in the human diet are mainly consumed in food together with macronutrients, this study investigated the in vivo absorption, metabolism, and distribution of polyphenolic compounds from the water extract of blackthorn flower (Prunus spinosa L.) in combination with a protein-enriched diet in the organs (small intestine, liver, kidney) of C57BL/6 mice. The bioaccumulation of polyphenol molecules, biologically available maximum concentrations of individual groups of polyphenol molecules, and their effect on the oxidative/antioxidative status of organs were also examined. The results of this study indicate increased bioabsorption and bioavailability of flavan-3-ols (EC, EGCG) and reduced absorption kinetics of certain polyphenols from the groups of flavonols, flavones, and phenolic acids in the organs of C57BL/6 mice after intragastric administration of the water extract of blackthorn flower (Prunus spinosa L.) in combination with a diet enriched with whey proteins. Furthermore, subchronic intake of polyphenols from the water extract of blackthorn flower (Prunus spinosa L.) in combination with a diet enriched with whey proteins induces the synthesis of total glutathione (tGSH) in the liver and superoxide dismutase (SOD) in the liver and small intestine. The results of this study suggest potential applications in the development of functional foods aimed at achieving the optimal health status of the organism and the possibility of reducing the risk of oxidative stress-related disease.

The effects of subchronic intake of magnesium hydrocarbonate-rich mineral water on body weight and cardiovascular variables in rats with streptozotocin: Induced diabetes

Background/Aim: Optimal intake of magnesium minerals is essential in maintaining the coordinated physiological functions of cells, tissues and organs. The importance of this element is reflected in the fact that it is the fourth most abundant cation in the human body, participating as a cofactor in more than three hundred enzymatic reactions. Its presence is necessary for the proper functioning of a number of vital functions, such as glycaemic control, the work of the heart and the vascular system and it can potentially play a role in the regulation of body weight. Aim of this study was to investigate the effects of subchronic intake of magnesium hydrocarbonate-rich water on changes in body weight, organ weight and cardiovascular variables in rats with streptozotocin-induced diabetes. Methods: Wistar rats (n = 28) were divided into 4 groups: two control groups, on tap water (TW-C, n = 7) and magnesium hydrocarbonate-rich water (MW-C, n = 7); and two experimental groups with streptozotocin-induced diabetes, on tap water (TW-DM, n = 7) and magnesium hydrocarbonate-rich water (MW-DM, n = 7). The values of body weight, organ weight and cardiovascular parameters were compared after 6 weeks between control groups of rats on subchronic treatment with tap water (TW-C) and magnesium hydrocarbonate-rich water (MW-C) and between groups with streptozotocin-induced diabetes on tap water (TW-DM) and with magnesium hydrocarbonate-rich water (MW-DM). Results: By comparing the values of cardiovascular parameters between groups, significant (p < 0.05) positive effects of magnesium hydrocarbonate-rich water were registered on the values of systolic and pulse blood pressure in diabetic rats fed with magnesium hydrocarbonate-rich water (MW-DM) compared to those fed with tap water (TW-DM). In contrast, no significant effect of magnesium hydrocarbonate on changes in body weight and organ weight was observed. Conclusion: Based on the results, the beneficial effects of magnesium hydrocarbonate-rich water in the regulation of blood pressure can be clearly observed. Potential effects on other cardiovascular variables and body weight and organ weight should be further investigated.

The effects of subchronic intake of magnesium hydro-carbonate-rich mineral water on cardiometabolic markers and electrolytes in rats with streptozotocin-induced diabetes

Background/Aim: Hypomagnesaemia is one of the most detected electrolyte abnormalities in diabetics. Modulation of numerous cardiovascular pathophysiological processes is a potential goal for anti-diabetic therapy. Magnesium supplementation prevents subclinical tissue magnesium deficiency, thus delaying the onset of metabolic imbalance in diabetes, but long-term effects of magnesium supplementation in chronic diabetes and numerous pathophysiological processes remain unknown. Aim of this study was to determine the effects of subchronic intake of magnesium hydrocarbonate-rich mineral water on cardiometabolic markers and electrolytes in rats with streptozotocin-induced diabetes. Methods: A total of 28 Wistar, male rats, body weight 160 g at start, were divided into four groups of 7 each: two controls, group that drank tap water and received a single ip injection of saline (0.9 % NaCl) (TW-C), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of saline (0.9 % NaCl) (MW-C); and two experimental groups with streptozotocin-induced diabetes, group that drank tap water and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (TW-DM), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (MW-DM). Results: Regarding the biochemical parameters, a decrease was observed in the MW-C group for vitamin B12 and proteins, while triglycerides were higher compared to the TW-C group. By comparing the haemostatic biomarkers between TW-C and MW-C groups, a statistically significant decrease was found for fibrinogen, while the electrolyte analysis showed an increase in phosphates for the MW-C group. Biochemical value comparison between TW-DM and MWDM groups showed that magnesium hydrocarbonate usage in diabetic rats did not significantly reduce glycaemia although the average glycaemic values were lower in the group treated with magnesium hydrocarbonate. Regarding the electrolyte values, a statistically significant decrease was observed for sodium, potassium and phosphate in the MW-DM group. The MW-DM group also showed a significant increase in iron value compared to TW-DM group. Conclusion: Subchronic intake of magnesium hydrocarbonate-rich mineral water, as a form of magnesium supplementation, did not cause a significant improvement in glycaemia or normalisation of diabetes-induced dyslipidaemia. This study showed the reduction of fibrinogen value, thus indicating the possibility of usage of this form of magnesium supplementation in different pro-thrombogenic conditions.

The toxicokinetics of Bromine in the body of laying hens under conditions of subchronic administration of sodium bromide diet

The aim of the scientific work was to study the toxicokinetics of Bromine in the body of laying hens under conditions of subchronic administration of sodium bromide diet. The subject of the study was the content of bromine in the organs and tissues of laying hens under conditions of subchronic administration of sodium bromide diet. The experiment was on laying hens. Three experimental and one control groups of animals were formed (n=15). The background indicator of the Bromine content in the compound feed was 2.0 mg/kg of feed. An aqueous solution of sodium bromide was added daily to the feed of the experimental groups for 28 days, and the observation of the poultry was continued for the next 14 days. The poultry of the experimental groups received bromine with feed at a dose of 10.0 mg/kg, II – 50.0 mg/kg, III – 250.0 mg/kg of feed. The selection of organs was under conditions of euthanasia of the poultry, by total exsanguination, during inhalation chloroform anesthesia on days 14, 28 and 42 of the experiment, 5 animals per group. The following research methods were used in the work: clinical (daily examination of the poultry), pathological (dissection and sampling of organs for research), toxicological (determination of Bromine content using X-ray fluorescence analysis), statistical (processing of the results was carried out by methods of variation statistics using the Statistica 6.0 software ( StatSoft Inc., USA)). It was found that bromine is absorbed most intensively in the small intestine: on the 28th day of the experiment, its content exceeded the control in group I by 6.5 times, in group II – 22 times, in III – 201.1 times. The study of the content of bromine in the liver, spleen, heart, and brain of three experimental groups testifies to the "material" accumulation of the element. In addition to the digestive tract, the excretion of bromine from the body of laying hens occurred through the kidneys, and possibly with exhaled air. In group III, on the 28th day, its content in the kidneys was 23.1 times higher than the control indicator, and on the 14th day in the lungs, the excess of the control indicator was 27.4 times. The excess of the element was not excreted from the body within 14 days after the cessation of the intake of sodium bromide with food. Key words: Bromine, subchronic intake, laying hens, bromine content in organs, toxicokinetics, sodium bromide.

Adaptogenic correction of free radical brain damage in subchronic exposure to sodium fl uoride

Introduction. Fluorine compounds in small doses, but with prolonged exposure, cause various disorders in organs at the cellular and molecular levels. Activation of free-radical processes plays an important role in the damaging eff ect of fl uorides. Th erefore, one of the most eff ective ways to limit fl uorine-induced damage is to directly aff ect free-radical processes using herbal preparations with antioxidant properties.The aim of the study is to study the eff ect of a dihydroquercetin-based drug on the activity of free radical processes in brain tissue under subchronic exposure to sodium fl uoride (NaF).Materials and methods. Th e work was performed on white male laboratory rats weighing 200-250 g. Th e rats were divided into 3 groups: 1 — control; 2 — rats with chronic exposure to sodium fl uoride (NaF) for 9 weeks; 3 — rats receiving a NAF solution with simultaneous administration of a complex drug based on dihydroquercetin at a dose of 3 mg/kg in 1% starch gel for 3, 6 and 9 weeks. The activity of free radical oxidation and antioxidant defense enzymes — superoxide dismutase (SOD) and catalase-was determined in the cerebral cortex. Th e level of expression of hypoxia-induced transcription factor HIF — 1A and inducible forms of proteins HSP72 and HSP32 were determined in the cytosolic fraction of brain tissue.Results. In the early stages of subchronic fl uoride exposure (1-3 weeks), the expression of protective proteins HIF-1α, HSP72, HSP32 and catalase was shown in the rat cortex, as a result of which the activity of free-radical processes was maintained at the control level. An increase in the timing of fl uoride intake to 9 weeks led to a decrease in antioxidant protection and signifi cant activation of free radical oxidation in brain tissue. Daily administration of a complex drug with dihydroquercetin for 3, 6 and 9 weeks to rats with subchronic fl uoride exposure led to a decrease in the severity of pro- and antioxidant balance disorders in the cerebral cortex. At the same time, the greatest protective eff ect of dihydroquercetin with fl uoride exposure was manifested by the 9th week of its administration.Conclusions. When subchronic intake of fl uorides in the body, the drug based on dihydroquercetin has a neuroprotective eff ect, which is manifested by an increase in the activity of antioxidant enzymes of fr ee radical oxidation and catalase and the resistance of the cortex to induced fr ee radical oxidation.

Nutritional and safety evaluation of locust (Caelifera) powder as a novel food material.

Insects are considered edible food resources with sufficient nutrients, but their nutrient composition and safety evaluation have not been fully investigated yet. In this study, we investigated the nutrient composition and the acute and sub-chronic toxicity of locust powder in male rats. In the acute oral toxicological experiment, rats were administered locust powder at a dose of 10 or 20g/kg/dose, followed by monitoring general signs of toxicity for 14 days. In the sub-chronic toxicological experiments, rats were fed with a diet containing 1% and 3% locust powder for 28 and 90 days. General signs of toxicity, body weight, plasma and blood components, weight and fat accumulation in tissues, and fecal fat excretion were investigated. The locust powder was rich in proteins, essential amino acids, minerals, and polyunsaturated fatty acids. In the acute toxicological experiment, no general signs of acute toxicity were observed at a dose of 20g/kg. In the sub-chronic toxicological experiments, parameters related to red blood cell were lowered by the 3% locust powder for 28 days, but not for 90 days. Liver lipid accumulation and fecal fat excretion were increased by the 3% locust powder for 90 days, but the liver lipids contents were considered to be within a nontoxic level. Cecum contents and cecum short-chain fatty acids were lowered by the locust powder, which can be caused by its fiber and fiber-like components. In conclusion, acute and sub-chronic intake of locust powder had little effect on general, biochemical, and hematological signs of toxicity in rats. PRACTICAL APPLICATION: Edible insects are increasingly viewed as new sustainable protein sources for human foods and livestock feeds worldwide because of their high nutritional balance, high food conversion rate, and environmental merits. Here, we have clarified that a locust powder contains high levels of protein, polyunsaturated functional fatty acids, and minerals (iron, zinc, and magnesium), and intake of locust powder (3% in diet) had little effects on general, biochemical, and hematological signs of toxicity in male rats. Locust as an edible insect, in powder form, can contribute to human dietary needs.

Subchronic Toxicity Assessment of Orally Administered Methanol (70%) Seed Extract of Abrus precatorius L. in Wistar Albino Rats.

Abrus precatorius L. is a famous medicinal plant of the family Fabaceae and is widely used in traditional medicine for the treatment of various ailments. However, there are limited toxicological data available regarding its safety following repeated exposure; therefore, the present study was designed to evaluate the 28-day subchronic toxicity of methanol (70%) crude extract of A. precatorius seeds in adult Wistar albino rats. A subchronic toxicity experiment was conducted by oral administration of graded doses (200 mg/kg and 400 mg/kg) of test extract daily for 28 days. Signs of toxicity, food and water consumption, body weight, and gross pathology as well as relative organ weight were evaluated. The toxic effects were also assessed using hematological and biochemical data followed by histopathological examination of various internal organs. All data collected were expressed as mean ± standard deviation. ANOVA followed by the Bonferroni test was used for data interpretation and p<0.05 was considered significant. No deaths or evident toxic signs were found during the experimental period. There were no significant differences in body weight, gross pathology, organ weight, or food and water consumption between the control and the treated groups. There were no treatment-related differences in hematological or biochemical indices. Moreover, no gross abnormalities or histological alterations were observed. The methanol extract of A. precatorius seeds was nontoxic in subchronic intake at the dosages tested. Thus, this study is expected to be beneficial for clinical and traditional applications for safe consumption and to utilize A. precatorius as a remedy at a recommended dosage.

Effects of Dark Chocolate Intake on Brain Electrical Oscillations in Healthy People.

Dark chocolate is rich in flavonoids that can have effects on body composition and cognitive performance. The aim of this study was to analyze the effects of acute and subchronic chocolate intake on electrical brain oscillations. A study with 20 healthy subjects (mean age of 24.15 years) and a control group with five subjects (mean age of 23.2 years) was carried out. In the acute effect study, the subjects’ intake was dark chocolate (103.72 mg/kg of body weight) rich in flavonoids and low in calories as in fasting. In the control group, the subjects intake was only low-calorie milk. For the subchronic effect, a daily dose of dark chocolate was given for eight days. The baseline electroencephalogram (EEG) was recorded before dark chocolate intake; at 30 min, the second EEG was carried out; on the eighth day, the third and fourth EEGs were performed before and after the last intake. In acute and subchronic intake, Delta Absolute Power (AP) decrease was observed in most brain regions (p < 0.05), except in the right fronto-centro-temporal regions. In the Theta band, there was a generalized decrease of the AP of predominance in the left fronto-centro-temporal regions. In contrast, an increase in AP was observed in the temporo-occipital regions in the Alpha band, and in the right temporal and parieto-occipital regions in the Beta band. The control group did not have significant changes in brain oscillations (p > 0.05). We concluded that acute and subchronic chocolate intake decreased the Delta and Theta AP and increased Alpha and Beta AP in most brain regions.

Effect of subchronic intake of green tea extract on liver of albino rat histomorphometric, ultrastructural and biochemical study.

There are conflicting reports on the effect of green tea extract (GTE) on the liver of animals. Some studies failed to show any adverse hepatic effects following administration of GTE to mice, rats, and dogs. Others reported severe hepatic necrosis, resulting in death in female Swiss-Webster mice following its administration. The aim of the study was to examine the subchronic toxicity of GTE on the liver of the adult male albino rats. Forty male adult Wistar albino rats were used in the study. The rats were divided into four groups; group I (control), group II (low-dose green tea), group III (medium-dose green tea) and group IV (high-dose green tea). Histological, biochemical and histomorphometric analyses were done. Mild hepatic affections were observed in group II. The affections were severe in groups III and IV. The central veins and hepatic sinusoids were congested. The hepatocytes were degenerated. Hypertrophy of the hepatic arteries, dilation of the bile ducts and cellular infiltration were clearly observed in the last two groups. Mild degenerative changes were observed in the hepatocytes in rat's group II; the cytoplasm was rarefied and vacuolated. Some mitochondria were ruptured. The blood sinusoids were congested. The rough endoplasmic retinaculum was fragmented in group III. More degenerative changes were observed in group IV; the hepatic architectures were lost with disruption of cell membranes. Most of the cell organelles were degenerated and most of mitochondria were ballooned. As compared to that of the control groups: the total serum protein values in groups II, III and IV showed a statistically significant decrease (12%, 20% and 21%, respectively), the mean area per cent of collagen fibres in groups III and IV increased 5 and 7 folds. Subchronic administration of GTE resulted in structural and functional affection of the rats' liver. The dose of 250 mg/kg/day seemed to be safe, while the doses of 500 mg/kg/day and 1000 mg/kg/day had deleterious effect being more evident in the latter dose.

Aspartame and Soft Drink-Mediated Neurotoxicity in Rats: Implication of Oxidative Stress, Apoptotic Signaling Pathways, Electrolytes and Hormonal Levels.

A significant association between fructose corn syrup in sweetened beverages consumption and increased risk of detrimental central nervous system effects has been recently reported. We hypothesized that the aspartame and soft drink induced disturbances in energy production and endocrine function, which play a role in the induction of brain damage. Therefore, we aimed to assess the effect of aspartame and soft drink on brain function and the link between energy status in the brain, oxidative stress and molecular pathways of apoptosis. Thirty rats were randomly assigned to drink water, aspartame (240mg/kg orally) and cola soft drinks (free access) daily for two months. Subchronic intake of aspartame and soft drink significantly disrupted the brain energy production, as indicated by inhibited serum and brain creatine kinase, specifically in soft drink-received rats. Moreover, they substantially altered serum electrolytes (increased Ca and Na, and depleted Cu, Fe, Zn and K levels), and accordingly the related hormonal status (increased T4 and PTH, and lowered T3 and aldosterone levels), particularly in soft drink-received rats reflecting brain damage. Additionally, significant increment of acetylcholine esterase activity concomitant with the reduction of antioxidant molecules (SOD, CAT, GSH-Px and GSH), and induction of malondialdehyde level are precisely indicative of oxidative brain damage. Brain mRNA transcripts of target genes showed that aspartame and soft drink induced upregulation of BAX, Casp3, P27 and Mdm2 (1.5-fold) and down-regulation of Bcl2, suggesting an activation of cellular apoptosis. Collectively, subchronic aspartame and soft drink-induced brain damage in rats may be driven via a mechanism that involves energy production disruption, electrolytes and hormonal imbalance, increased oxidative stress and activation of molecular pathway of neuronal apoptosis.

Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status

Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines.

Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

Background:Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects.Methods:Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire.Results:Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged.Conclusions:In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents.

Effect of Sodium Metabisulphite on Blood Metabolic Status of Wistar Rats

The objective of this work was to determine the sodium metabisulphite (NaMBS) subchronic toxicity used as a food additive in Algeria. Three groups of female Wistar rats were treated with 0.25%, 1% and 4% of NaMBS in their drinking water for 90 days. An immunization protocol was conducted during the experiment. Mortality, comportmental and weight modifications, and food and water consumption were recorded. At the end of the experiment, the control and experiment rats were killed, and their blood and organs were removed. Immunoglobulin levels were evaluated; biochemical and hematological parameters were investigated. Our results showed that the administration of NaMBS at 1% and 4% had significant effects on body weight, food and water consumed. There was an increase in biochemical parameters (calcium, urea, creatinine, uric acid, transaminases) and decrease immunoglobulin levels. The hematology revealed a decrease in red blood cells and hemoglobin, as well as leucocytosis. Physiological study showed enlarged spleen, kidney, liver and stomach. In light of our results, we can conclude that subchronic intake of NaMBS 1% and 4% seems to alter immune function, biochemical, hematological and physiological para-meters in Wistar rats.

Fluoxetine and Sleep EEG: Effects of a Single Dose, Subchronic Treatment, and Discontinuation in Healthy Subjects

The goals of the current study were to evaluate whether a single dose of fluoxetine causes qualitatively different changes in sleep architecture and NREM sleep EEG than subchronic administration in healthy subjects and to determine degree and duration of such changes after the single dose and after discontinuation from subchronic administration. Our hypothesis was that subchronic intake should cause changes qualitatively different from the single dose and that such changes could be sufficiently long-lived to suggest the possibility of a dosing in intervals of several days. Ten healthy volunteers first took one single 60-mg dose of fluoxetine and a week later started to take a 40-mg dose every morning for three weeks. Sleep laboratory nights included two nights before and four nights after the single dose and every second night for two weeks after discontinuation from subchronic administration. The single dose caused only a slight increase in drug plasma concentrations but relatively clear changes in sleep structure. After discontinuation from subchronic administration, sleep quality indices normalized quickly (within 2-4 days), whereas REM latency and spectral power effects correlated with total SSRI plasma concentration and normalized more slowly, corresponding to the drug plasma half-life of about 10 days. The REM fraction of the sleep period showed a rebound, whereas the delta sleep ratio did not correlate with drug plasma levels and yet remained increased after the medication interval. Thus, the only qualitative difference seen between acute and subchronic medication was the initial sleep disturbance. REM latency and especially the delta sleep ratio remained increased for several days after discontinuation from subchronic administration, indicating the possibility of a less-than-daily maintenance medication after an initial daily interval. Finally, the pattern of change observed for the delta sleep ratio indicates that it may be due to secondary, adaptive effects possibly linked to the antidepressant effect of fluoxetine in depressed patients.

Effect of Panax ginseng on age-related changes in the spontaneous motor activity and dopaminergic nervous system in the rat.

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.

Effect of Panax Ginseng on Age-Related Changes in the Spontaneous Motor Activity and Dopaminergic Nervous System in the Rat

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.

Influence of Subchronic Intake of Melatonin at Various Times of the Day on Fatigue and Hormonal Levels: A Placebo‐Controlled, Double‐Blind Trial

In a double-blind study, melatonin (50 mg) or placebo was administered daily to 25 subjects at 9 am or 7 pm for 1 week. Self-rated fatigue as evaluated by the Stanford Sleepiness Scale (SSS) was significantly increased during the 3 hours following melatonin intake in the morning, whereas, after administration in the evening, no difference between melatonin and placebo could be distinguished. Sleep onset latency slightly decreased in both melatonin groups without reaching statistical significance. No cumulative effects on sleep or behavior were observed. Twelve pituitary and peripheral hormones measured under baseline and partly (in the evening groups) under stimulated conditions before and after the trial did not change. The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.