Alteration of Ethanol Reward by Prior Mephedrone Exposure: The Role of Age and Matrix Metalloproteinase-9 (MMP-9).

Mephedrone, a synthetic cathinone, is widely abused by adolescents and young adults. The aim of this study was to determine: (i) whether prior mephedrone exposure would alter ethanol reward and (ii) whether age and matrix metalloproteinase-9 (MMP-9) are important in this regard. In our research, male Wistar rats at postnatal day 30 (PND30) received mephedrone at the dose of 10 mg/kg, i.p., 3 times a day for 7 days. To clarify the role of MMP-9 in the mephedrone effects, one mephedrone-treated group received minocycline, as an MMP-9 antagonist. Animals were then assigned to conditioned place preference (CPP) procedure at PND38 (adolescent) or at PND69 (adult). After the CPP test (PND48/79), expression of dopamine D1 receptors (D1R), Cav1.2 (a subtype of L-type calcium channels), and MMP-9 was quantified in the rat ventral striatum (vSTR). The influence of mephedrone administration on the N-methyl-D-aspartate glutamate receptors (NMDAR) subunits (GluN1, GluN2A, and GluN2B) was then assessed in the vSTR of adult rats (only). These results indicate that, in contrast with adolescent rats, adult rats with prior mephedrone administration appear to be more sensitive to the ethanol effect in the CPP test under the drug-free state. The mephedrone effect in adult rats was associated with upregulation of D1R, NMDAR/GluN2B, MMP-9, and Cav1.2 signaling. MMP-9 appears to contribute to these changes in proteins expression because minocycline pretreatment blocked mephedrone-evoked sensitivity to ethanol reward. Thus, our results suggest that prior mephedrone exposure differentially alters ethanol reward in adolescent and adult rats.

Over-the-counter antipyretics use among children from Southeastern Poland.

BACKGROUND: Over-the-counter (OTC) drugs are becoming increasingly popular. However, little is known about parents' practices concerning the use of OTC antipyretics in children. This paper aimed to study the habits and knowledge of parents regarding the use of OTC antipyretics in their offspring, considering the demographic and socioeconomic characteristics of the families. MATERIAL AND METHODS: A multiple-purpose survey was conducted anonymously among 229 parents of patients hospitalised in the Department of Paediatrics, University Children's Hospital, Krakow. Each parent answered 23 questions regarding OTC antipyretics use in his/her hospitalised child throughout the whole child's life. The data was statistically analysed. RESULTS: OTC antipyretics are administered to their children by 92% of parents. In the vast majority (87%), health care professionals or a leaflet were the sources of information on the drug and its dosage. Parents also used information from TV or the Internet (27%) and friends and family (30%), especially those in the younger age group. Families with high socioeconomic status were more likely to use health care professionals' advice for drug knowledge. Parents of children with allergic diseases made less use of nonmedical sources of knowledge. CONCLUSIONS: The majority of parents use OTC antipyretic drugs in their children. However, a high percentage of people using nonmedical sources of information is of concern. It is necessary to educate caregivers and to build the parents' awareness that they take an active role in their child's treatment. It would be useful to create generally available recommendations for home treatment.

Aversive Learning Deficits and Depressive-Like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: The Protective Effect of Rapamycin.

Fetal alcohol spectrum disorders (FASDs) are one of the most common consequences of ethanol exposure during pregnancy. In adulthood, these disorders can be manifested by learning and memory deficits and depressive-like behavior. Ethanol-induced oxidative stress may be one of the factors that induces FASD development. The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. We investigated whether mTOR-dependent or mTOR-independent mechanisms are engaged in this phenomenon. Thus, Rapamycin-a selective inhibitor of mTORC1, Torin-2-a non-selective mTORC1/mTORC2 inhibitor, and FK-506-a drug that impacts oxidative stress in an mTOR-independent manner were used. Behavioral tests were performed in adult (PND60-65) rats using a passive avoidance (PA) task (aversive learning and memory) and forced swimming test (FST) (depressive-like behaviors). In addition, the biochemical parameters of oxidative stress, such as lipid peroxidation (LPO), as well as apurinic/apyrimidinic (AP)-sites were determined in the hippocampus and prefrontal cortex in adult (PND65) rats. The rat FASD model was induced by intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4-9 (an equivalent to the third trimester of human pregnancy). All substances (3 mg/kg) were given 30 min before ethanol. Our results show that neonatal ethanol exposure leads to deficits in context-dependent fear learning and depressive-like behavior in adult rats that were associated with increased oxidative stress parameters in the hippocampus and prefrontal cortex. Because these effects were completely reversed by Rapamycin, an mTORC1 inhibitor, this outcome suggests its usefulness as a preventive therapy in disorders connected with prenatal ethanol exposure.

CE-123, a novel dopamine transporter inhibitor, attenuates locomotor hyperactivity and improves cognitive functions in rat model of fetal alcohol spectrum disorders.

Perinatal alcohol exposure can lead to fetal alcohol spectrum disorders (FASD), usually first diagnosed in childhood, that are characterized by hyperactivity, impulsivity and learning and memory disability, among others. To test the hypothesis that dopamine signaling is one of the main factors underlying these impairments, a new atypical dopamine transporter (DAT) inhibitor, CE-123 (1, 3 or 10 mg/kg) was assessed for its potential to overcome the ethanol-induced behavioral effects in a rat model of FASD. In the present study, neonatal rats were exposed to alcohol intubations across the neonatal period (postnatal day (PND)4-9, the third trimester equivalent of human gestation) and, after weaning, the animals (male rats) were assigned randomly to three groups. The first group was tested at PND21 (hyperactivity test). A second group was tested at PND45 (anxiety test), at PND47 (locomotor activity test), at PND49 (spatial cognitive test in the Barnes maze) and PND50 (reversal learning in the Barnes maze). The third group was tested at PND50 (dopamine receptor mRNA expression). Our results support the hypothesis that dopamine signaling is associated with FASD because the dopamine (D1, D2 and D5) receptor mRNA expression was altered in the striatum, hippocampus and prefrontal cortex in adult rats exposed to ethanol during neonatal period. CE-123 (3 and 10 mg/kg) inhibited the hyperactivity and ameliorated (10 mg/kg) the impairment of reversal learning in alcohol-exposed rats. Thus, these findings provide support that CE-123 may be a useful intervention for same of the deficits associated with neonatal ethanol exposure.

Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period.

Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4-9 (an equivalent to the third trimester of human pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were evaluated in adult (PND60-70) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit's up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.

Rapamycin Improves Recognition Memory and Normalizes Amino-Acids and Amines Levels in the Hippocampal Dentate Gyrus in Adult Rats Exposed to Ethanol during the Neonatal Period.

The mammalian target of rapamycin (mTOR), a serine/ threonine kinase, is implicated in synaptic plasticity by controlling protein synthesis. Research suggests that ethanol exposure during pregnancy alters the mTOR signaling pathway in the fetal hippocampus. Thus, we investigated the influence of pre-treatment with rapamycin, an mTORC1 inhibitor, on the development of recognition memory deficits in adult rats that were neonatally exposed to ethanol. In the study, male and female rat pups received ethanol (5 g/kg/day) by intragastric intubation at postanatal day (PND 4-9), an equivalent to the third trimester of human pregnancy. Rapamycin (3 and 10 mg/kg) was given intraperitoneally before every ethanol administration. Short- and long-term recognition memory was assessed in the novel object recognition (NOR) task in adult (PND 59/60) rats. Locomotor activity and anxiety-like behavior were also evaluated to exclude the influence of such behavior on the outcome of the memory task. Moreover, the effects of rapamycin pre-treatment during neonatal ethanol exposure on the content of amino-acids and amines essential for the proper development of cognitive function in the dentate gyrus (DG) of the hippocampus was evaluated using proton magnetic resonance spectroscopy (1H MRS) in male adult (PND 60) rats. Our results show the deleterious effect of ethanol given to neonatal rats on long-term recognition memory in adults. The effect was more pronounced in male rather than female rats. Rapamycin reversed this ethanol-induced memory impairment and normalized the levels of amino acids and amines in the DG. This suggests the involvement of mTORC1 in the deleterious effect of ethanol on the developing brain.

Effects of Mephedrone and Amphetamine Exposure during Adolescence on Spatial Memory in Adulthood: Behavioral and Neurochemical Analysis.

A synthetic cathinone, mephedrone is widely abused by adolescents and young adults. Despite its widespread use, little is known regarding its long-term effects on cognitive function. Therefore, we assessed, for the first time, whether (A) repeated mephedrone (30 mg/kg, i.p., 10 days, once a day) exposure during adolescence (PND 40) induces deleterious effects on spatial memory and reversal learning (Barnes maze task) in adult (PND 71-84) rats and whether (B) these effects were comparable to amphetamine (2.5 mg/kg, i.p.). Furthermore, the influence of these drugs on MMP-9, NMDA receptor subunits (GluN1, GluN2A/2B) and PSD-95 protein expression were assessed in adult rats. The drug effects were evaluated at doses that per se induce rewarding/reinforcing effects in rats. Our results showed deficits in spatial memory (delayed effect of amphetamine) and reversal learning in adult rats that received mephedrone/amphetamine in adolescence. However, the reversal learning impairment may actually have been due to spatial learning rather than cognitive flexibility impairments. Furthermore, mephedrone, but not amphetamine, enhanced with delayed onset, MMP-9 levels in the prefrontal cortex and the hippocampus. Mephedrone given during adolescence induced changes in MMP-9 level and up-regulation of the GluN2B-containing NMDA receptor (prefrontal cortex and hippocampus) in young adult (PND 63) and adult (PND 87) rats. Finally, in adult rats, PSD-95 expression was increased in the prefrontal cortex and decreased in the hippocampus. In contrast, in adult rats exposed to amphetamine in adolescence, GluN2A subunit and PSD-95 expression were decreased (down-regulated) in the hippocampus. Thus, in mephedrone-but not amphetamine-treated rats, the deleterious effects on spatial memory were associated with changes in MMP-9 level. Because the GluN2B-containing NMDA receptor dominates in adolescence, mephedrone seems to induce more harmful effects on cognition than amphetamine does during this period of life.

Delirium Post-Stroke: Short- and Long-Term Effect on Depression, Anxiety, Apathy and Aggression (Research Study-Part of PROPOLIS Study).

BACKGROUND: Stroke patients are particularly vulnerable to delirium episodes, but very little is known about its subsequent adverse mental health outcomes. The author's objective was to explore the association between in-hospital delirium and depression, anxiety, anger and apathy after stroke. METHODS: A total of 750 consecutive patients with acute stroke or transient ischemic attack, were screened for delirium during hospitalization. Patients underwent mental health evaluation in hospital, 3 and 12 months post-stroke; depression, apathy, anxiety and anger were the outcomes measured at all evaluation check points. RESULTS: Delirium was an independent risk factor for depression (OR = 2.28, 95%CI 1.15-4.51, p = 0.017) and aggression (OR = 3.39, 95%CI 1.48-7.73, p = 0.004) at the hospital, for anxiety 3 months post-stroke (OR = 2.83, 95%CI 1.25-6.39, p = 0.012), and for apathy at the hospital (OR = 4.82, 95%CI 2.25-10.47, p < 0.001), after 3 (OR = 3.84, 95%CI 1.31-11.21, p = 0.014) and 12 months (OR = 4.95, 95%CI 1.68-14.54, p = 0.004) post stroke. CONCLUSIONS: The results of this study confirm, that mental health problems are very frequent complications of stroke. Delirium in the acute phase of stroke influences mental health of patients. This effect is especially significant in the first months post-stroke and vanishes with time, which suggests that in-hospital delirium might not be a damaging occurrence in most measures of mental health problems from a long-term perspective.

Impact of the metabotropic glutamate receptor7 (mGlu7) allosteric agonist, AMN082, on fear learning and memory and anxiety-like behavior.

The present study was conducted to evaluate the influence of AMN082, the metabotropic glutamate receptor subtype 7 (mGlu7) allosteric agonist on different stages of memory processes connected with fear conditioning in the passive avoidance (PA) learning task in mice and negative emotional state (anxiety-like) induced by ethanol- and morphine-withdrawal in the elevated plus maze (EPM) test in rats. To perform the PA test, AMN082 (1.25, 2.5 and 5 mg/kg, i. p.) was injected to interfere with (or inhibit) acquisition, consolidation, and retrieval processes. The retention latency in each group was recorded using a step-through passive avoidance task 24 h after training. In turn, in ethanol- and morphine-withdrawal rats, the influence of AMN082 on anxiety-like behavior was estimated in the EPM test 24 h- (ethanol) and 72- h (morphine) after the last dose of repeated drug administrations. In all experimental groups, AMN082 at the dose of 5 mg/kg significantly decreased the step-through latency of long-term memory in the PA task. These AMN082 effects were reversed by MMPIP (10 mg/kg), the antagonist of mGlu7 receptor. AMN082 (2.5 and 5 mg/kg) also decreased ethanol- and morphine withdrawal-induced anxiety-like behavior in the EPM test, and this AMN082 (5 mg/kg) effect was counteracted by MMPIP pretreatment. Taken together, the results show that mGlu7 is involved in fear learning to the context and anxiety-like state connected with unpleasant experiences after ethanol- and morphine withdrawal in rodents. However, it appears that functional dissociation exists between these two AMN082 effects.

Variability of water chemistry in Tundra Lakes, Petuniabukta Coast, Central Spitsbergen, Svalbard.

Samples of water from small tundra lakes located on raised marine terraces on the eastern coast of Petuniabukta (Ebbadalen, Central Spitsbergen) were examined to assess the changes in water chemistry that had occurred during the summer seasons of 2001-2003 and 2006. The unique environmental conditions of the study region include the predominance of sedimentary carbonate and sulphate rocks, low precipitation values, and an active permafrost layer with a maximum thickness of 1.2 m. The average specific electric conductivity (EC) values for the three summer seasons in the four lakes ranged from 242 to 398 µS cm(-1). The highest EC values were observed when the air temperature decreased and an ice cover formed (cryochemical effects). The ion composition was dominated by calcium (50.7 to 86.6%), bicarbonates (39.5 to 86.4%), and sulphate anions. The high concentrations of HCO(3) (-), SO(4) (2-), and Ca(2+) ions were attributed to the composition of the bedrock, which mainly consists of gypsum and anhydrite. The average proportion of marine components in the total load found in the Ebbadalen tundra lake waters was estimated to be 8.1%. Precipitation supplies sulphates (as much as 69-81%) and chlorides (14-36%) of nonsea origin. The chief source of these compounds may be contamination from the town of Longyearbyen. Most ions originate in the crust, the active layer of permafrost, but some are atmospheric in origin and are either transported or generated in biochemical processes. The concentrations of most components tend to increase during the summer months, reaching a maximum during freezing and partially precipitating onto the bottom sediments.

[Risk factors of retinopathy of prematurity in newborns treated in neonatal intensive care unit of University Children's Hospital Collegium Medicum Jagiellonian University]. / Czynniki ryzyka rozwoju retinopatii wczesniaków u pacjentów Oddzialu Patologii i Intensywnej Terapii Noworodka Uniwersyteckiego Szpitala Dzieciecego Collegium Medium Uniwersytetu Jagiellonskiego.

BACKGROUND: A persistent progress in perinatal care and a large increase in infants' survival rate have been observed recently. As a result, the number of neonates requiring ophthalmologic examinations due to retinopathy of prematurity (ROP) increased as well. METHOD: A retrospective survey including 206 neonates with mean birth weight 1342 g and mean gestational age 30 weeks. MATERIAL: Three groups: 1) without ROP--165 infants (80.1%); 2) with ROP not requiring treatment--13 infants (6.3%); 3) with prethreshold and threshold ROP requiring cryotherapy--28 infants (13.6%) were analysed. RESULTS: Threshold ROP was not observed in infants with gestational age > 32 weeks and/or birth weight > 1500 g. Cryotherapy was applied between the 6th and 18th weeks of life (Mo: 12). The procedure was applied at postmenstrual age between the 34th and 45th weeks of life (Mo: 38). The correlation of ROP with the following factors was observed: length of mechanical ventilation (Me in the studied groups: 6; 22; 33 days respectively; p < 0.01), length of oxygen therapy (Me: 27; 58; 70 days; p < 0.01), number of blood transfusions in first month of life (Me: 2; 4; 4; p < 0.01), minimum pO2 (average: 37.2; 30.2; 29.2 mmHg p < 0.01), pO2 oscillation (measured as SD) (Me: 10.25; 13.2; 15.4 mmHg p < 0.016) and maximal pCO2 (average: 52.5; 56.8; 66.5 p < 0.01) between the 2nd and 4th weeks of life. CONCLUSION: Monitoring of pO2 and pCO2 in infants in the 1st month of life reduce the risk of ROP development. Infants born before the 32nd week of gestational age belong to high risk group and require very systematic ophthalmologic examination. The current prophylactic examination schedule for ROP for more mature infants may be changed.

Trisomy 8 mosaicism syndrome.

Authors present the case of a 15-year-old boy assessed for Marfan syndrome for many years. The child was treated because of skeletal defects, mild mental deficiency and dysmorphic features of face. Chromosomal analysis showed a trisomy 8 mosaicism.