Sleep deprivation, pain and prematurity: a review study / Privação do sono, dor e prematuridade: um estudo de revisão

The aim was to describe current reports in the scientific literature on sleep in the intensive care environment and sleep deprivation associated with painful experiences in premature infant. A systematic search was conducted for studies on sleep, pain, premature birth and care of the newborn. Web of Knowledge, MEDLINE, LILACS, Cochrane Library, PubMed, EMBASE, Scopus, VHL and SciELO databases were consulted. The association between sleep deprivation and pain generates effects that are observed in the brain and the behavioral and physiological activity of preterm infants. Polysomnography in intensive care units and pain management in neonates allow comparison with the first year of life and term infants. We have found few references and evidence that neonatal care programs can influence sleep development and reduce the negative impact of the environment. This evidence is discussed from the perspective of how hospital intervention can improve the development of premature infants.

O objetivo foi descrever o estado atual na literatura científica sobre privação do sono associado a experiências dolorosas no prematuro e o papel na evolução do sono em ambiente de terapia intensiva. Realizou-se uma busca sistemática para estudos sobre sono, dor, prematuridade e programas de atenção ao neonato. Foram consultados as bases Web-of-Knowledge, MEDLINE, LILACS, Biblioteca Cochrane, PubMed, EMBASE, Scopus, BVS e SciELO. A associação entre privação do sono e dor gera efeitos que são observados na atividade cerebral, fisiológica e comportamental dos prematuros. A polissonografia nas unidades intensivas e o manejo da dor em neonatos permitem comparação no primeiro ano de vida com crianças nascidas a termo. Encontraram-se poucas evidências de que programas de cuidado neonatal podem influenciar o desenvolvimento do sono e diminuir o impacto negativo do ambiente. Estas evidências são discutidas na perspectiva de como a intervenção hospitalar pode melhorar o desenvolvimento do prematuro.

Effect of sildenafil citrate on behavior and excitatory and inhibitory amino acids levels in albino rat's brain

Sildenafil is an active cGMP-specific phosphodiesterase type 5 inhibitor that is effective in the treatment of male erectile dysfunction. None of the previous studies have measured sildenafil or its possibly related neurochemical changes, but mainly they related their finding to sildenafil associated behavior changes. In this work, behavioral and brain neurochemical changes [excitatory and inhibitory neurotransmitters] associated with acute administration of sildenafil using male albino rats were investigated. Rats were divided into three groups [n=6]; group1 received saline [1ml/kg], group 2 received single doses of sildenafil [1.5mg/kg], while group 3 received single doses of sildenafil [100mg/kg]. Administration was via the intraperitoneal route. Behavior scores using EPM and brain homogenate for neurotransmitters evaluation by HPLC were carried out 60min after administration. Sildenafil did not produce any changes in behavior using the EPM test; also it did not alter the brain levels of excitatory, inhibitory and dopamine. Sildenafil produced dose dependent decreases in plasma dopamine level by mechanism[s] needs more neurochemical investigation. The chronic effect of sildenafil should be taken into consideration.

The effects of ingested aluminium on brain cytochrome oxidase activity / Efectos de la ingestión de aluminio sobre la actividad de la oxidasa citocrómica del cerebro

Aluminium has a unique combination of physical and chemical properties which has enabled man to put this metal to very wide and varied use. However, prolonged exposure to aluminium ions may lead to adverse health effects. In this study, we evaluated the effects of dietary aluminium on the protein composition and the intrinsic activity of cytochrome oxidase (COX) for brain mitochondria. New Zealand white rabbits were maintained on a diet of commercial rabbit pellets and distilled water for a period of 12 weeks. For the experimental group, AlCl3, 330mg/kg/L was added to the drinking water. When compared to the control, mitochondria isolated from the brains of the AlCl3 fed rabbits showed no change in Km but an approximate 35% decrease in both the low and high affinity Vmax values. Also, whereas the protein composition of the mitochondria from both sources appeared to be normal, isolation of highly purified COX proved to be difficult and for the AICI3 fed rabbits, a number of the enzyme's low molecular weight subunits were absent. These results appear to confirm a relationship between long term aluminium consumption and low brain COX activity; they further suggest that an altered COX structure may be the cause of the low enzymic activity.

El aluminio posee una combinación única de las propiedades físicas y químicas que ha permitido al ser humano hacer un uso amplio y variado de este metal. Sin embargo, un número de estudios recientes, sugiere que la exposición prolongada a los iones de aluminio puede tener efectos nocivos sobre la salud. En el presente estudio, evaluamos los efectos del aluminio dietético sobre la composición proteínica y la actividad intrínseca de la oxidasa citocrómica (COX) para la mitocondria cerebral. Conejos blancos de Nueva Zelanda, fueron mantenidos con una dieta de alimento para conejos y agua destilada por un período de 12 semanas. Para el grupo experimental AlCl3, 330mg/kg/L fueron añadidos al agua potable. En comparación con el grupo de control, las mitocondrias aisladas de los cerebros de los conejos alimentados con AlCl3 no mostraron cambios en Km pero hubo una disminución de aproximadamente 35% tanto en los valores Vmax de baja y alta afinidad. Por otro lado, mientras que la composición proteica de las mitocondrias de ambas fuentes parecía ser normal, resultó difícil aislar el COX altamente purificado y un número de enzimas de subunidades de bajo peso molecular MMMM estuvieron ausentes. Estos resultados parecen confirmar una relación entre el consumo de aluminio a largo plazo y la baja actividad del COX del cerebro. Asimismo, sugieren que una alteración de la estructura del COX puede ser la causa de una baja actividad enzimática.

Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera.

BACKGROUND & OBJECTIVES: The monoaminergic systems which exert a modulatory role in memory processing, are disturbed in Alzheimer's disease (AD) and Moringa oleifera (MO) has been shown to exert its effect in CNS by altering the brain monoamines. The present study aims to see whether chronic oral treatment of ethanolic extract of MO leaves can alter the brain monoamines (norepinephrine, dopamine and serotonin) in distinct areas of brain in rat model of AD caused by intracerebroverticle (ICV) infusion of colchicine and hence can provide protection against monoaminergic deficits associated with AD. METHODS: Rats were given ICV infusion of colchicine (15 microg/5microl) and MO leaf alcoholic extract was given in various doses. The effective dose was standardized by radial arm maze (RAM) training. From the selected dose of 250 mg/kg body weight, the biochemical estimations and EEG studies were performed. RESULTS: Stereotaxic ICV infusion of colchicine significantly impaired the RAM performance together with decrease in norepinephrine (NE) level in cerebral cortex (CC), hippocampus (HC) and caudate nucleus (CN). Dopamine (DA) and serotonin (5-HT) levels were decreased in CC, HC and CN. The EEG studies showed a decrease in beta and alpha waves and increase in biphasic spike wave pattern in experimental Alzheimer rat model. Treatment with MO extract markedly increased the number of correct choices in a RAM task with variable alteration of brain monoamines. The EEG studies showed an increase in beta waves and a decrease in spike wave discharges. INTERPRETATION & CONCLUSION: Our results showed that brain monoamines were altered discreetly in different brain areas after colchicine infusion in brain. After treatment with MO, leaf extract the monoamine levels of brain regions were restored to near control levels. Our findings indicated that MO might have a role in providing protection against AD in rat model by altering brain menoamine levels and electrical activity.

Ethanol Intake during Lactation Alters Milk Nutrient Composition and Growth and Mineral Status of Rat Pups

Lactating Wistar rats were fed a liquid diet containing either ethanol [ethanol-fed group (EFG)] or an isocaloric amount of carbohydrate [pair-fed group (PFG)] from day 1 postpartum up to day 14 of lactation, to investigate micro/macronutrient milk composition and the mineral status of pups. EFG presented a reduction of daily milk production and milk composition was significantly higher in protein and lower in carbohydrate, while the lipid content was similar to that of PFG. When compared to PFG, the milk of EFG had a decreased proportion of C22:6 n-3 fatty acid and an increase in medium-chain fatty acids and of several minerals. Pups of EFG showed reduced growth and a lower concentration of Cu and Sr in plasma and lower concentrations of Ca, P and Cl, and higher concentrations of Cd in the brain. We conclude that maternal EtOH intake greatly impairs lactational performance and modifies the mineral status of pups.

Contaminación por monóxido de carbono: un problema de salud ambiental / Carbon monoxide contamination: an environmental health problem

El monóxido de carbono es considerado uno de los mayores contaminantes de la atmósfera terrestre. Sus principales fuentes productoras responsables de aproximadamente 80 por ciento de las emisiones, son los vehículos automotores que utilizan como combustible gasolina o diesel y los procesos industriales que utilizan compuestos del carbono. Esta sustancia es bien conocida por su toxicidad para el ser humano. Sus efectos tóxicos agudos incluida la muerte han sido estudiados ampliamente; sin embargo, sus potenciales efectos adversos a largo plazo son poco conocidos. En los últimos años, los estudios de investigación experimentales en animales y epidemiológicos en humanos han evidenciado relación entre población expuesta en forma crónica a niveles medios y bajos de monóxido de carbono en aire respirable y la aparición de efectos adversos en la salud humana especialmente en órganos de alto consumo de oxígeno como cerebro y corazón. Se han documentado efectos nocivos cardiovasculares y neuropsicológicos en presencia de concentraciones de monóxido de carbono en aire inferiores a 25 partes por millón y a niveles de carboxihemoglobina en sangre inferiores a 10 por ciento. Las alteraciones cardiovasculares que se han descrito son hipertensión arterial, aparición de arritmias y signos electrocardiográficos de isquemia. Déficit en memoria, atención, concentración y alteraciones del movimiento tipo parkinsonismo, son los cambios neuropsicológicos con mayor frecuencia asociados a exposición crónica a bajos niveles de monóxido de carbono y carboxihemoglobina.

Carbon monoxide is considered to be a major factor contaminating earths atmosphere. The main sources producing this contamination are cars using gasoline or diesel fuel and industrial processes using carbon compounds; these two are responsible for 80 percent of carbon monoxide being emitted to the atmosphere. This substance has a well-known toxic effect on human beings and its acute poisonous effects (including death) have been widely studied; however, its long-term chronic effects are still not known. During the last few years, experimental research on animals and studies of human epidemiology have established the relationship between chronic exposure to low and middle levels of carbon monoxide in breathable air and adverse effects on human health, especially on organs consuming large amounts of oxygen such as the heart and brain. Harmful cardiovascular and neuropsychological effects have been documented in carbon monoxide concentration in air of less than 25 ppm and in carboxyhaemoglobin levels in blood of less than 10 percent. The main cardiac damage described to date has been high blood pressure, cardiac arrhythm and electrocardiograph signs of ischemia. Lack of memory, attention, concentration and Parkinson-type altered movement are the neuropsychological changes most frequently associated with chronic exposure to low levels of carbon monoxide and carboxyhaemoglobin.

Effect of intracerebroventricular methotrexate on brain amines.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.

O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão / The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

OBJETIVO: As mudanças no eixo hipotálamo-pituitária-adrenal (HPA) são características da depressão. Devido aos efeitos dos glicocorticóides serem mediados por receptores intracelulares, como os receptores de glicocorticóides (RGs), inúmeros estudos examinaram o número e/ou função dos RGs em pacientes com depressão. MÉTODOS: Os autores fazem uma revisão das evidências científicas dos estudos que têm consistentemente demonstrado que a função dos RGs está prejudicada na depressão maior, em conseqüência da redução da resposta do eixo HPA ao feedback negativo mediado pelos RGs e a um aumento na produção e secreção de HLC em várias regiões cerebrais, sugerindo que esses mecanismos estão envolvidos na etiologia da depressão e no tratamento antidepressivo. RESULTADOS: Esta revisão faz um resumo da literatura atual sobre RG na depressão e sobre o impacto dos antidepressivos nos RGs em estudos clínicos e pré-clínicos, e dá suporte ao conceito de que a sinalização deficiente dos RGs é parte fundamental na fisiopatogenia da depressão, na ausência de evidências claras de redução na expressão dos RGs. Embora os efeitos dos antidepressivos nos hormônios glicocorticóides e seus receptores sejam relevantes para a ação terapêutica dessas drogas, os mecanismos moleculares subjacentes a esses efeitos ainda não estão esclarecidos. Estudos indicam que os antidepressivos têm efeitos diretos nos RGs, levando a uma melhora da função e a um aumento da expressão dos RGs. Nós propomos que, em humanos, os antidepressivos podem inibir os transportadores de esteróides localizados na barreira hemato-liquórica e nos neurônios, como o complexo de resistência a múltiplas drogas glicoproteína-p ("multidrug resistance p-glycoprotein"), e podem aumentar o acesso do cortisol ao cérebro e o feedback negativo mediado por glicocorticoides no eixo HPA. CONCLUSÃO: O aumento da ação do cortisol no cérebro pode ser uma abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.

Postnatal changes in the brain lipids, glycolipids and gangliosides of rats exposed to arrack/ethanol during gestation and lactation.

Effects of exposure of an alcoholic beverage (arrack and its equivalent quantity of alcohol throughout pregnancy and lactation on brain lipids were investigated. Female rats were exposed to arrack (12.00 ml/kg body weigh/day) and ethanol (4.00 g/kg body weight day) before conception and throughout gestation and lactation. For 21 days pups were nursed by their own mothers, afterwards they were fed normal laboratory feed. We found that the level of cholesterol, phospholipids, triacylglycerols, free fatty acids, cerebrosides, ceramide dihexosides, ceramide polyhexosides, sulfatids,, mono and diglycosyl diglycerides and gangliosides were increased in the brain of 21st and 45th day pups. The alterations in the glycolipid profile of the brain persisted even when pups were not directly exposed to alcohol. These alterations in the glycolipid and ganglioside metabolism may be associated with the developmental abnormalities of the brain seen in FAS. The elevation produced in the glycolipid profile of arrack administered pups were more than that caused by its equivalent quantity of ethanol. This suggested an interaction of congeners in the arrack with the alcohol.

Age-related regional difference of interleukin-1 expression in rat brain after lipopolysaccharide treatment

Aging is associated with altered immune responses including dysregulation of cytokine production. Of cytokines, interleukin-1 (IL-1) family has been primarily involved with central nervous system. To evaluate the age-related different response of IL-1 family following peripheral administration of lipopolysaccharide (LPS), immunohistochemical study of IL-1beta and IL-1 receptor expression was performed on Sprague-Dawley rat brain. Experimental animals were divided into four groups; saline-treated young (3-5 months) and old (over 24 months), and LPS-treated young and old groups. After intraperitoneal (i.p.) injection of LPS, three to five rats within each group were killed at 1, 2, 4, 8 and 16 hr. After fixation in 4% neutral buffered formalin, the brain slices were paraffin-embedded. Immunohistochemical staining using labelled streptavidin biotin was performed. The results showed that IL-1beta immunoreactivity was seen in the endothelial cell of pons in both LPS-reated young and old rats, with slightly longer persistency in old group. IL-1RI immunoreactivity appeared initially in the neurons of cerebral cortex in LPS-treated old group, compared with predominantly the cerebellum in LPS-treated young group. In conclusion, our study shows that there is age-related, different neuronal localization of IL-1RI expression at different points of time after LPS treatment.

Role of dopamine in the modulation of adrenal gland responses in the osmotically stressed pigeons, Columba livia.

Salt loading on pigeons (C. livia) had stimulatory effects on brain amines (dopamine and 5-hydroxytryptamine), corticosterone, norepinephrine and epinephrine contents of adrenal gland. Conjoint administration of dopamine with hypertonic saline restored the brain amines and corticosterone of adrenal gland, but had no effect on catecholamine (CAM) contents of adrenal medulla. The excessive release of CAM in the plasma indicates sympathetic stimulation after both the treatments.

Changes in the brain cholesterol level induced by different cholesterol derivatives in albino rats

Changes in the level of cholesterol in albino rats CNS [cerebrum, cerebellum, brain stem, spinal cord] were evaluated following the administration of three reported derivatives of cholesterol 3beta-acetoxy-cholest 5-ene, 3beta-acetoxy-6-nitro..cholest-5-ene and 3beta-acethxy-5-cholestan-6-one. Experiments were conducted on four groups of six albino rats weighing 250-300 gm. Control rats were administered normal saline ip while the other three experimental groups were given 0.3 mg/kg bw of steroidal solution ip which was prepared in peanut oil

Effects of sex steroids on the concentrations of some brain neurotransmitters in male and female rats: some new observations.

Concentrations of some neurotransmitters, viz. noradrenaline (NA), 5-hydroxytryptamine (5-HT), dopamine (DA), histamine (H) and gamma aminobutyric acid (GABA) in a part of brain consisting of medulla, pons, mid brain, thalamus and hypothalamus were measured in ovariectomized (OVx), intact (+Te) and castrated male (Tex) rats both without injecting estrogen (E) or E and progesterone (P) as well as after E and E+P administration. Some effects, (which, as far as we are aware of) have not been previously reported, were noted (in addition to other already documented observations). These include: (i) castration in males causes a fall of the level of GABA, NA, 5-HT and DA, (ii) E therapy also causes fall of the levels of GABA, NA and 5-HT and thus E therapy produces similar results like those of bilateral orchidectomy, (iii) P therapy not only reverses the fall of (GABA) but raises it more than the normal value, (iv) P therapy, it appears (although faintly), retrieve to some extent the fall of NA level due to E therapy, (v) Like the OVx rats, castrated as well as intact rats also showed a fall in the 5-HT level with E treatment but showed a rise when treated by E followed by P, (vi) In between the castrated males and castrated females, the concentrations of all these brain neurotransmitters differ. The probable significances have been discussed.

In vivo effects of isatin on certain enzymes, lipids & serotonergic system of rat brain.

Isatin (10 microM) strongly inhibited the activity of rat brain monoamine oxidase-B (MAO-B) in vitro. At millimolar concentrations (1-10 mM) it inhibited brain acetylcholinesterase (AChE) and sodium, potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity also. However, isatin did not affect these enzymes after both acute and chronic treatments in vivo. Administration of isatin to rats at 300 mg/kg body weight for 2 and 6 h significantly raised brain serotonin levels. Chronic treatment for 20 days resulted in enhanced brain glycolipids and plasmalogen levels. There was no change in the levels of 5-hydroxy indole acetic acid (5 HIAA), phospholipids, cholesterol and gangliosides under these conditions.

Effect of pirprofen on prostaglandins, norepinephrine, serotonin and dopamine content of rat brain

Estimation of prostaglandin E [2] [PGE [2]] level and of the chemical transmitters, serotonin [5-HT], norepinephrine [NE] and dopamine IDA content was performed in different parts of the brain of rats given pirprofen [36 mg/kg] by I.M. injection. The results showed a decrease in PGE [2] content in the thalamus and hypothalamus, and in dopamine content of the striatum with a significant increase in the nerotonin level of the mid brain, however, there was insignificant inecrease in the norepinephrine [NE] level of pons and medulla. 5-HT/NE and 5-HT/DA ratios were found to be raised by pirprofen. These data may help to explain the mechanism of activities of pirprofen as a non-steroidal anti-inflammatory drug

Effects of topically applied sulphur mustard on tissue glycogen, blood glucose, lactate and pyruvate in mice.

Bis-2-Chloroethyl sulphide, commonly known as sulphur mustard (SM) or mustard gas, an alkylating agent, is frequently used as a chemical warfare agent. Inhibition of glycolysis has been related to skin injury and cell death. The effects of SM on tissue glycogen, blood glucose, lactate/pyruvate ratio were investigated in the present study. After a single dermal application of 1.0 LD50 SM in mice, a significant hyperglycemia was observed at 24 hr post exposure. There was a corresponding decrease in liver glycogen content, with no alteration in glycogen content of brain, muscles and kidney. Blood pyruvate and lactate levels were not appreciably altered.

Effect of soman administration on beta-esterases in blood, liver microsomes and brain regions of rats.

Activities of enzymes cholinesterase (ChE) and carboxylesterase (CaE) were assayed in serum, liver microsomes and three regions of brain, viz; cerebrum, cerebellum and brain stem (with mid brain) in male albino rats at 0.5 and 2 h periods after administration of 1/2 LD 50 dose of soman (0.22 mg/kg) intraperitoneally in olive oil as vehicle. At 0.5 h, in serum, ChE activity declined to 33% of its initial level whereas CaE activity was almost completely inhibited. However, in the liver microsomes at this period, ChE activity was greatly inhibited (18% of initial level) whereas CaE activity was nearly unaffected. At 2 h period, both the enzymes in the serum were almost completely inhibited. In the brain regions (excepting in cerebellum), both the enzymes were nearly similarly inhibited (by 55% to 65% of the initial level) at both the periods. The time related differential response of these two beta-esterases in acute soman intoxication probably occurred in the peripheral tissues like blood and liver but not in the CNS.

Influence of selenium supplementation during chelation of lead in rats.

The influence of selenium supplementation during chelation therapy to reduce body burden and toxicity of lead was investigated in rats. Selenium had marginal effects on liver, kidney and blood lead decorporation by calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA) and activation of inhibited delta- aminolevulinic acid dehydratase (ALAD) activity by calcium trisodium diethylenetriamine penta acetic acid (CaNa3DTPA). Selenium supplementation however, had no influence on lead induced inhibition of renal and hepatic transaminases and alkaline phosphatase. The results suggest that selenium supplementation slightly augments lead mobilization by chelating drugs.